Fused imidazo[1,2-A]pyridines

ABSTRACT

PCT No. PCT/JP96/00975 Sec. 371 Date Oct. 21, 1997 Sec. 102(e) Date Oct. 21, 1997 PCT Filed Apr. 10, 1996 PCT Pub. No. WO96/33195 PCT Pub. Date Oct. 24, 1996Compounds of the formula: which are useful as anti-ulcer agent are provided.

This is a 371 national stage application of PCT/JP96/00975, filed onApr. 10, 1996.

FIELD OF THE INVENTION

The present invention relates to novel fused imidazo[1,2-a]pyridines andmedicaments containing them. More particularly, it relates to fusedimidazo[1,2-a]pyridines useful for treatment of peptic ulcers, which arecharacterized by having a (hetero)aryl group on the 2-position and anamino group on the 3-position, and pharmaceutically acceptable salts orsolvates thereof, and pharmaceutical compositions containing them.

BACKGROUND OF THE INVENTION

It has been explained that peptic ulcers like gastric and duodenalulcers are developed due to collapse of balance between aggressivefactors (gastric acid, pepsin, etc.) and defensive factors (blood flow,mucus, mucosal resistance, mucosal protection, etc.). Peptic ulcers areusually subjected to medical treatment, and various medications areapplied thereto. The drugs for peptic ulcer therapy may be divided intotwo types, one being inhibitors of aggressive factors, the other beingpromoters of defensive factors, and they are used properly according tothe type of diseases. Currently, histamine H₂ -blockers (e.g.cimetidine, ranitidine, etc.) are generally used in the clinical stageas inhibitors against aggressive factors. However, it has been reportedthat there are refractory ulcers, and that the H₂ -blockers possessadverse side effects, such as antiandrogen action and inhibitory actionagainst liver metabolizing enzymes. Recently, it has been found that H⁺/K⁺ -ATPase is associated with the final step for acid secretion, and ithas been suggested that benzimidazoles having inhibitory action on thisenzyme, such as omeprazole, are useful as anti-ulcer drugs. However,palindromia of ulcer is a problem remained unsolved. Furthermore, otherproblems requiring an improvement exist, such as development ofcarcinoid, and an interaction with other drugs, which decreases liverclearances for diazepam and fenitoin. On the other hand, it iswell-known that the promoters of defensive factors show limited healingrate as compared with the inhibitors of aggressive factors, and that theformer provides delayed disappearance of subjective symptom. Thus,anti-ulcer drugs presently available are not satisfactory, anddevelopment of promising new anti-ulcer drugs has being desired.

The purpose of the present invention is to find compounds having bothinhibitory action against aggressive factors and promoting action onmucosal defensive factors, and to provide more promising anti-ulcerdrugs.

European Patent Publication No.0165545 and U.S. Pat. No. 4,468,400disclose tricyclic compounds which have similar structures to thecompounds of the present invention. However, they don't disclosecompounds which have the same substituents as the substituents on thecompounds of the present invention. European Patent PublicationsNo.0033094, No.0068378 and No.0204285 disclose non-fusedimidazo[1,2-a]pyridines which, on account of their antisecretory andcytoprotective actions, are intended to use for the treatment of ulcer.

DETAILED DESCRIPTION

The present inventors have now discovered, after extensive studies, thatnovel fused imidazo[1,2-a]pyridines bearing a (hetero)aryl group on the2-position and an amino group on the 3-position, and pharmaceuticallyacceptable salts or solvates thereof have noteworthy pharmacologicalproperties and they are advantageously different from knownimidazo[1,2-a]pyridines above-noted in their-pharmacological activities.The present invention is based on such findings.

Accordingly, one object of the present invention is to provide novelfused imidazo[1,2-a]pyridines and pharmaceutically acceptable salts orsolvates thereof, which show an inhibitory action on gastric acidsecretion and a protective action of gastric mucosa.

Another object of the invention is to provide pharmaceuticalcompositions comprising, as an active ingredient, said fusedimidazo[1,2-a]pyridine, or a pharmaceutically acceptable salt or solvatethereof.

The compound of the invention is represented by the following generalformula (I): ##STR2## wherein ring A and ring B each independentlyrepresent an aromatic ring selected from benzene, thiophene, furan orpyrrole ring; R¹ is hydroxyl group, halogen atom, lower alkyl groupwhich may be halogenated, lower alkoxy group or acyloxy group, krepresents 0, 1, 2 or 3; R² and R³ may be the same or different and eachrepresent hydrogen atom, alkenyl group, acyl group, alkoxycarbonyl groupor lower alkyl group which may have substituent(s) selected from thegroup consisting of 1) halogen atom, 2) hydroxyl group, 3) lower alkoxygroup, 4) lower alkylthio group, 5) alkylsulfinyl group, 6)alkoxycarbonyl group, 7) carbamoyl group, 8) alkylamino group and 9)aryl group, or R² and R³, together with the nitrogen atom to which theyare attached, may form a 5- or 6-membered monocyclic heterocyclic ring,or R² and R³, together with the nitrogen atom to which they areattached, may form an alkylideneamino group or arylalkylideneaminogroup; R⁴ and R⁵ each independently represent halogen atom, cyano group,hydroxyl group, carboxyl group, alkoxycarbonyl group, acyl group,alkylamino group, aryl group, acyloxy group, carbamoyloxy group, loweralkyl group which may have substituent(s) selected from the groupconsisting of 1) hydroxyl group, 2) lower alkoxy group, 3) aryl groupand 4) aryloxy group, lower alkoxy group which may have substituent(s)selected from the group consisting of 1) hydroxyl group, 2) lower alkoxygroup, 3) lower alkoxycarbonyl group and 4) aryl group, or loweralkylthio group which may be substituted with aryl group; m represents0, 1 or 2; n represents 0, 1 or 2; the dotted line, together with thesolid line, represents a single or double bond, provided that plural R⁴s may be attached to the same carbon atom.

The terms used herein are defined below. Substituents on thecompounds(I) of the present invention have the following significances,whether the substituents exist alone or constitute part of other group.

"Benzene, thiophene, furan or pyrrole ring represented by ring A" areshown below. ##STR3##

"Benzene, thiophene, furan or pyrrole ring represented by ring B" areshown below. ##STR4##

"Halogen atom" may include a fluorine atom, a chlorine atom, a bromineatom and an iodine atom.

"Lower alkyl group" means straight, branched or cyclic alkyl grouphaving 1 to 6 carbon atoms, and may include, for example, methyl group,ethyl group, propyl group, isopropyl group, butyl group, isobutyl group,sec-butyl group, tert-butyl group, pentyl group, isopentyl group,neopentyl group, tert-pentyl group, 1-methylbutyl group, 2-methylbutylgroup, 1,2-dimethylpropyl group, hexyl group, isohexyl group,1-methylpentyl group, 2-methylpentyl group, 3-methylpentyl group,1,1-dimethylbutyl group, 1,2-dimethylbutyl group, 2,2-dimethylbutylgroup, 1,3-dimethylbutyl group, 2,3-dimethylbutyl group,3,3-dimethylbutyl group, 1-ethylbutyl group, 2-ethylbutyl group,1,2,2-trimethylpropyl group, 1-ethyl-1-methylpropyl group,1-ethyl-2-methylpropyl group, cyclopropyl group, cyclobutyl group,cyclopentyl group, 2-methylcyclopentyl group, cyclohexyl group and thelike. Preferable lower alkyl groups include an alkyl group having 1 to 4carbon atoms, in particular, lower alkyl group having 1 to 3 carbonatoms.

"Acyl group" may include a residue of an organic acid such as aliphaticsaturated carboxylic acid, aliphatic unsaturated carboxylic acid andarylcarboxylic acid, and specific examples are lower alkanoyl groupcarrying, for example, formyl group, acetyl group, propionyl group,butyryl group, isobutyryl group, hexanoyl group, bromoacetyl group,trifluoroacetyl group, methoxyacetyl group, butoxyacetyl group,phenoxyacetyl group, 4-bromomethylphenylacetyl group,4-methoxyphenylacetyl group, 1-naphthylacetyl group, 3-pyridylacetylgroup, 3-chloropropionyl group, 3-bromopropionyl group,3-(methylthio)propionyl group, 3-ethoxypropionyl group,3-(3,4-dimethoxyphenyl)propionyl group, 3-carboxypropionyl group,3-benzoylpropionyl group, 4-chlorobutyryl group, 3-acetylbutyryl group,succinyl group, cyclopentylacetyl group, 6-bromohexanoyl group and thelike; lower alkenoyl group carrying, for example, acryloyl group,2-furylacryloyl group, crotonoyl group, 3-methylcrotonoyl group,cinnamoyl group, 4-methoxycinnamoyl group, methoxymaleoyl group,methoxyfumaroyl group and the like; arylcarbonyl group such as benzoylgroup, 4-pentylbenzoyl group, p-anisoyl group, o-anisoyl group,3,5-bis(trifluoromethyl)benzoyl group, 4-bromobenzoyl group,4-butoxybenzoyl group, 4-chlorobenzoyl group, 3-chlorobenzoyl group,4-chloromethylbenzoyl group, 4-cyanobenzoyl group, 3,4-dichlorobenzoylgroup, 3,5-dichlorobenzoyl group, 2,4-difluorobenzoyl group,3,4-dimethoxybenzoyl group, 4-ethoxybenzoyl group, 3-fluorobenzoylgroup, 4-isopropylbenzoyl group, 3-(trifluoromethyl)benzoyl group,3,4,5-trimethoxybenzoyl group, 3,4-dimethylbenzoyl group, m-toluoylgroup, o-toluoyl group, p-toluoyl group, 1-naphthoyl group, 2-naphthoylgroup, 1-bromo-2-naphthoyl group and the like; or heteroarylcarbonylgroup such as 2-thenoyl group, 3-thenoyl group, 5-methyl-2-thenoylgroup, 2-furoyl group, 5-bromo-2-furoyl group, nicotinoyl group,isonicotinoyl group, 6-methylpicolinoyl group, 3-methyl-2-benzo[b]furoylgroup, quinoline-2-carbonyl group and the like. Preferable acyl groupsare residues of aliphatic carboxylic acids, in particular, residues ofaliphatic saturated carboxylic acids.

"Alkenyl group" means straight or branched alkenyl group having 2 to 6carbon atoms, and may include, for example vinyl group, allyl group,1-propenyl group, isopropenyl group, 2-methyl-1-propenyl group,1-butenyl group, 2-butenyl group, 3-butenyl group, 2-ethyl-1-butenylgroup, 3-methyl-2-butenyl group, 1,3-butadienyl group, 1-pentenyl group,2-pentenyl group, 3-pentenyl group, 4-pentenyl group,4-methyl-3-pentenyl group, 1-hexenyl group, 2-15 hexenyl group,3-hexenyl group, 4-hexenyl group, 5-hexenyl group and the like.Preferable alkenyl groups are alkenyl groups having 2 to 3 carbon atoms.

"Lower alkoxy group" means alkoxy group having 1 to 6 carbon atoms, suchas methoxy group, ethoxy group, propoxy group, isopropoxy group, butoxygroup, isobutoxy group, sec-butoxy group, tert-butoxy group, pentyloxygroup, isopentyloxy group, neopentyloxy group, tert-pentyloxy group,1-methylbutoxy group, 2-methylbutoxy group, 1,2-dimethylpropoxy group,hexyloxy group, isohexyloxy group, 1-methylpentyloxy group,2-methylpentyloxy group, 3-methylpentyloxy group, 1-ethylbutoxy group,2-ethylbutoxy group, 1,2,2,-trimethylpropoxy group,1-ethyl-1-methylpropoxy group, 1-ethyl-2-methylpropoxy group and thelike. Preferable alkoxy groups are alkoxy groups having 1 to 4 carbonatoms, in particular, alkoxy groups having 1 to 3 carbon atoms.

"Lower alkylthio group" may include methylthio group, ethylthio group,propylthio group, isopropylthio group, butylthio group, isobutylthiogroup, sec-butylthio group, tert-butylthio group, pentylthio group,isopentylthio group, neopentylthio group, tert-pentylthio group,l-methylbutylthio group, 2-methylbutylthio group and the like.

"Alkylsulfinyl group" means the above-mentioned "alkyl group" to which asulfinyl group is bonded, and it may include, for example,methylsulfinyl group, ethylsulfinyl group, isopropylsulfinyl group,butylsulfinyl group and the like.

"Lower alkoxycarbonyl group" means the above-mentioned "lower alkoxygroup" to which a carbonyl group is bonded, and it may include, forexample, methoxycarbonyl group, ethoxycarbonyl group, propoxycarbonylgroup, isopropoxycarbonyl group, butoxycarbonyl group, isobutoxycarbonylgroup, sec-butoxycarbonyl group, tert-butoxycarbonyl group,pentyloxycarbonyl group, isopentyloxycarbonyl group,3-methylpentyloxycarbonyl group, 2,3-dimethylbutoxycarbonyl group,3,3-dimethylbutoxycarbonyl group, 2-ethylbutoxycarbonyl group and thelike.

"Carbamoyl group" may include carbamoyl group, dimethylcarbamoyl group,ethylcarbamoyl group, diethylcarbamoyl group, allylcarbamoyl group,cyclopentylcarbamoyl group, hexylcarbamoyl group, N-(4-ethoxycarbonyloxyphenyl)carbamoyl group, N-(4-trifluoromethylphenyl)carbamoyl groupand the like.

"Alkylamino group" may include methylamino group, ethylamino group,dimethylamino group, diethylamino group, dipropylamino group,N-methyl-N-ethylamino group, N-methyl-N-propylamino group,N-ethyl-N-propylamino group and the like.

"Aryl group" may include phenyl group, 2-chlorophenyl group,3-fluorophenyl group, 4-bromo-3-methylphenyl group, 4-methoxyphenylgroup, 2-thienyl group, 2-chloro-5-thienyl group, 3-methyl-2-furylgroup, 4-methyl-5-thiazolyl group, 4-chloro-2methyl-5-oxazolyl group,1-methyl-2-imidazolyl group, 1-bromo-2-naphthyl group,6-methyl-2-naphthyl group, 8-methoxy-1-naphthyl group,3-methyl-2-benzo[b]furyl group, 5-chloro-3-benzo[b]thienyl group and thelike.

"5- or 6-membered cyclic ring formed together with the nitrogen atom"may include, for example, pyrrolyl group, 2-pyrrolinyl group,3-pyrrolinyl group, pyrrolidinyl group, imidazolidinyl group,pyrazolidinyl group, succinimide group, piperidino group, piperazinylgroup, morpholino group, glutarimide group and the like.

"Alkylideneamino group" may include ethylideneamino group,propylideneamino group, isopentylideneamino group,2-methylpentylideneamino group, 3,3-dimethylbutylideneamino group,2-ethylbutylideneamino group and the like.

"Arylalkylideneamino group" may include benzylideneamino group,4-bromobenzylideneamino group, 2-chloro-6-fluorobenzylideneamino group,2-methylbenzylideneamino group, 4-methylbenzylideneamino group,2,5-dimethylbenzylideneamino group, 2,4,6-trimethylbenzylideneaminogroup, 3-methoxybenzylideneamino group, 3,4-dimethoxybenzylideneaminogroup, 2-phenethylideneamino group, (1-bromo-2-naphthyl)methylideneaminogroup, cinnamylideneamino group and the like.

"Acyloxy group", "carbamoyloxy group" or "aryloxy group" respectivelymeans the above-mentioned "acyl group", "carbamoyl group" or "arylgroup", to which an oxygen atom is bonded.

The novel compounds of the present invention represented by the formula(I) may be classified into the following two-types according to thepartial structure of the compounds. Thus, when ring B is benzene ring,the compounds of the invention can be represented by the formula (I-1),and when ring B is thiophene, furan or pyrrole ring, the compounds ofthe invention can be represented by the formula (I-2). ##STR5## whereinring A, R¹, R², R³, R⁴, R⁵, k, m and n are as defined above, any one ofZ¹, Z², or Z³ represents a hetero-atom selected from sulfur, oxygen ornitrogen atom, and the others represent carbon atom.

Preferred compounds of the invention represented by the formula (I) mayinclude the compounds (I-1) wherein ring B is benzene ring, or thecompounds I-2) wherein ring B is thiophene, furan, or pyrrole ring, andeither Z¹ or Z³ represents a hetero atom selected from sulfur, oxygen ornitrogen atom, and the other represents carbon atom. In particular, ringB preferably represents benzene or thiophene ring.

Preferred compounds of the invention represented by the formula (I) mayinclude those wherein R¹ represents halogen atom, lower alkyl groupwhich may be halogenated, or lower alkoxy group. In particular, R¹preferably represents lower alkyl group having 1 or 2 carbon atoms.

Further preferred compounds of the invention represented by the formula(I) may include those wherein R² and R³ may be the same or different andeach represent hydrogen atom, alkenyl group or lower alkyl group whichmay have substituent(s) selected from the group consisting of halogenatom, lower alkoxy group, lower alkylthio group and aryl group, or R²and R³, together with the nitrogen atom to which they are attached, mayform a 5- or 6-membered monocyclic heterocyclic ring. Additionalpreferred compounds are those wherein at least one of R² and R³represents hydrogen atom.

Other preferred compounds of the invention represented by the formula(I) are those wherein ring A is benzene, thiophene, furan or pyrrolering; ring B is benzene or thiophene ring; one of R¹ is halogen atom,lower alkyl group which may be halogenated, or lower alkoxy group; k is1 or 2; R² and R³ may be the same or different and each representhydrogen atom, alkenyl group or lower alkyl group which may havesubstituent(s) selected from the group consisting of halogen atom, loweralkoxy group, lower alkylthio group and aryl group, or R² and R³,together with the nitrogen atom to which they are attached, may form a5- or 6-membered monocyclic heterocyclic ring.

Especially preferable compounds of the invention represented by theformula (I) are those wherein ring A is benzene, thiophene, furan orpyrrole ring; and at least one of the substituent(s) on ring A islocated at ortho-position with respect to the binding site where ring Ais bound to other part of the molecule including ring B moiety, asillustrated below: ##STR6## wherein R¹ and R⁶ represent halogen atom,lower alkyl group which may be halogenated, or lower alkoxy group; k'represents 0 or 1; and Z represents a hetero-atom selected from sulfur,oxygen or nitrogen atom; ring B represents benzene or thiophene ringrepresented by the formula I-2) in which either Z¹ or Z³ representssulfur atom; R² is hydrogen atom; R³ is hydrogen atom, alkenyl group orlower alkyl group which may have substituent(s) selected from the groupconsisting of halogen atom, lower alkoxy group, lower alkylthio groupand aryl group; and the dotted line, together with the solid line,represents a double bond.

Most preferable compounds of the invention represented by the formula(I) are those wherein ring A is benzene, thiophene, furan or pyrrolering; the substituent R⁶ on the ring A represented by theabove-illustrated formulae is lower alkyl group having 1 or 2 carbonatoms; k' is 0 or 1; ring B represents benzene or thiophene ringrepresented by the formula I-2) in which Z¹ is sulfur atom; R² and R³are each a hydrogen atom; R⁴ and R⁵ are each halogen atom, lower alkylgroup, lower alkoxy group or lower alkylthio group; m is 0, 1 or 2; n is0, 1 or 2; and the dotted line, together with the solid line, representsa double bond.

The following may be mentioned as examples of the compounds according tothe invention to be singled out in particular:

3-amino-9-chloro-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline,

3-amino-5-methyl-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline,

3-amino-9-methyl-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline,

3-amino-5-ethyl-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline,

3-amino-5-isopropyl-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline,

3-amino-5-methoxy-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline,

3-amino-9-methoxy-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline,

3-amino-2-(2-methylphenyl)-9-(methylthio)imidazo[2,1-a]isoquinoline,

3-amino-9-fluoro-5-methyl-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline,

3-amino-2-(4-fluoro-2-methylphenyl)-5-methylimidazo[2,1-a]isoquinoline,

3-amino-2-(5-fluoro-2-methylphenyl)-9-methoxyimidazo[2,1-a]isoquinoline,

3-amino-2-(2-methyl-3-thienyl)imidazo[2,1-a]isoquinoline,

3-amino-5-methyl-2-(2-methyl-3-thienyl)imidazo[2,1-a]isoquinoline,

3-amino-2-(2-methyl-3-thienyl)-9-(methylthio)imidazo[2,1-a]isoquinoline,

3-amino-5-methoxy-2-(2-methyl-3-thienyl)imidazo[2,1-a]isoquinoline,

3-amino-9-fluoro-5-methyl-2-(2-methyl-3-thienyl)imidazo[2,1-a]isoquinoline,

3-amino-2-(2-ethyl-3-thienyl)imidazo[2,1-a]isoquinoline,

3-amino-2-(2,5-dimethyl-3-thienyl)-9-fluoroimidazo[2,1-a]isoquinoline,

3-amino-2-(2,5-dimethyl-3-thienyl)-5-methylimidazo[2,1-a]isoquinoline,

3-amino-2-(2,5-dimethyl-3-thienyl)-9-methoxyimidazo[2,1-a]isoquinoline,

3-amino-2-(5-chloro-2-methyl-3-thienyl)-5-methylimidazo[2,1-a]isoquinoline,

3-amino-2-(5-ethyl-2-methyl-3-thienyl)-5-methylimidazo[2,1-a]isoquinoline,

3-amino-2-(2-chloro-3-methyl-4-thienyl)-5-methylimidazo[2,1-a]isoquinoline,

3-amino-2-(2-methyl-3-furyl)-5-methylimidazo[2,1-a]isoquinoline,

3-amino-2-(2,5-dimethyl-3-furyl)-5-methylimidazo[2,1-a]isoquinoline,

3-amino-5-methyl-2-(2-methylphenyl)imidazo[1,2-a]thieno[3,2-c]pyridine,

3-amino-5-ethyl-2-(2-methylphenyl)imidazo[1,2-a]thieno[3,2-c]pyridine,

3-amino-5,8-dimethyl-2-(2-methylphenyl)imidazo[1,2-a]thieno[3,2-c]pyridine,

3-amino-2-(4-fluoro-2-methylphenyl)-5-methylimidazo[1,2-a]thieno[3,2-c]pyridine,

3-amino-5-methyl-2-(2-methyl-3-thienyl)imidazo[1,2-a]thieno[3,2-c]pyridine,

3-amino-8-methyl-2-(2-methyl-3-thienyl)imidazo[1,2-a]thieno[3,2-c]pyridine,

3-amino-5,6-dimethyl-2-(2-methyl-3-thienyl)imidazo[1,2-a]thieno[3,2-c]pyridine,

3-amino-2-(4-methyl-3-thienyl)imidazo[1,2-a]thieno[3,2-c]pyridine,

3-amino-2-(2-ethyl-3-thienyl)-5-methylimidazo[1,2-a]thieno[3,2-c]pyridine,

3-amino-2-(2-methoxy-3-thienyl)-5-methylimidazo[1,2-a]thieno[3,2-c]pyridine

3-amino-2-(5-chloro-2-methyl-3-thienyl)-5-methylimidazo[1,2-a]thieno[3,2-c]pyridine,

3-amino-2-(2,5-dimethyl-3-thienyl)-5-methylimidazo[1,2-a]thieno[3,2-c]pyridine,

3-amino-2-(2,5-dimethyl-3-thienyl)-5-ethylimidazo[1,2-a]thieno[3,2-c]pyridine,

3-amino-2-(5-ethyl-2-methyl-3-thienyl)imidazo[1,2-a]thieno[3,2-c]pyridine,

3-amino-2-(5-methoxy-2-methyl-3-thienyl)-5-methylimidazo[1,2-a]thieno[3,2-c]pyridine,

3-amino-2-(2-chloro-3-methyl-4-thienyl)-5-methylimidazo[1,2-a]thieno[3,2-c]pyridine,

3-amino-5-methyl-2-(2-methyl-3-furyl)imidazo[1,2-a]thieno[3,2-c]pyridine,

3-amino-2-(2-methoxy-3-furyl)imidazo[1,2-a]thieno[3,2-c]pyridine,

3-amino-5-methyl-2-(1-methyl-2-pyrrolyl)imidazo[1,2-a]thieno[3,2-c]pyridine

3-amino-2-(2,5-dimethyl-3-thienyl)furo[3,2-c]imidazo[1,2-a]pyridine,

3-amino-7-(4-chlorobenzyl)-2-(2-methylphenyl)imidazo[1,2-a]pyrrolo[3,2-c]pyridine,

3-amino-5-methyl-2-(2-methyl-3-thienyl)imidazo[1,2-a]thieno[3,4-c]pyridine,

3-amino-2-(2-chlorophenyl)imidazo[1,2-a]thieno[2,3-c]pyridine,

3-amino-5-methyl-2-(2-methylphenyl)imidazo[1,2-a]thieno[2,3-c]pyridine,

3-amino-5-methyl-2-(2-methyl-3-thienyl)imidazo[1,2-a]thieno[2,3-c]pyridine,

3-amino-2-(2,5-dimethyl-3-thienyl)imidazo[1,2-a]thieno[2,3-c]pyridine,

3-amino-2-(2,5-dimethyl-3-furyl)-5-methylimidazo[1,2-a]thieno[2,3-c]pyridine,

3-amino-2-(1-methyl-2-pyrrolyl)imidazo[1,2-a]thieno[2,3-c]pyridine,

Suitable pharmaceutically acceptable salts of the compound (I) mayinclude conventional salts used for drugs, such as those formed with analkali metal (e.g. sodium, potassium, etc.) or an alkaline earth metal(e.g. magnesium, calcium, etc.) or an inorganic base(e.g. aluminum,etc.), and those formed with an organic base (e.g. ethylamine,propylamine, diethylamine, triethylamine, morpholine, pyridine,piperidine, N-ethylpiperidine, diethanolamine, cyclohexylamine, etc.),those formed with a basic amino acid (e.g. lysine, ornithine etc.), anammonium salt, those formed with a mineral acid (e.g. hydrochloric acid,sulfuric acid, phosphoric acid, hydrobromic acid, etc.), those formedwith an organic acid (e.g. acetic acid, oxalic acid, succinic acid,citric acid, maleic acid, malic acid, fumaric acid, tartaric acid,picric acid, methanesulfonic acid, ethanesulfonic acid, etc.), and thoseformed with an acidic amino acid (e.g. glutamic acid, aspartic acid,etc.).

The compounds (I) of the present invention and pharmaceuticallyacceptable salts thereof may include their solvates (e.g. water,ethanol, etc.) and polymorphism, in case that they can be isolated.

The compounds (I) of the invention include stereoisomers, opticalisomers or geometrical isomers thereof.

The compounds of the invention may be prepared by various methods.Typical methods are shown below. ##STR7## wherein R⁴, R⁵, Z¹, Z², Z³, mand n are as defined above; X is a leaving group to be replaced byamine, R⁷ is hydrogen atom, amino group, arylalkyl group which may havesubstituent(s), or alkyl group which may have substituent(s).

Among the compounds represented by the formula (II), thienopyridines, inwhich any one of Z¹, Z² or Z³ is a sulfur atom, can be preparedaccording to methods known to those skilled in the art [see, forexample, Journal of Chemical Society, Perkin Transactions 1, p1390,(1975)], or analogous methods thereto. Furopyridines, any one of Z¹, Z²or Z³ is an oxygen atom in the formula (II), can also be preparedaccording to methods known to those skilled in the art [see, forexample, Journal of Heterocyclic Chemistry, 19, p1207, (1982)], oranalogous methods thereto. Pyrrolopyridines, any one of Z¹, Z² or Z³ isa nitrogen atom in the formula (II), can be prepared according tomethods known to those skilled in the art [see, for example,Tetrahedron, 32, p773, (1976)], or analogous methods thereto. Theleaving group X to be replaced by amine, may include, for example,alkoxy group, alkylthio group, alkylsulfinyl group, alkylsulfonyl groupand halogen atom. Suitable leaving group X is halogen atom, inparticular, chlorine atom.

Among the compounds represented by the formula (IV), thienopyridines, inwhich any one of Z¹, Z² or Z³ is a sulfur atom, can be preparedaccording to methods known to those skilled in the art [see, forexample, Journal of Heterocyclic Chemistry, 9, p843, (1972), Journal ofHeterocyclic Chemistry, 30, p289, (1993)], or analogous methods thereto.Furopyridines, any one of Z¹, Z² or Z³ is an oxygen atom in the formula(IV), can be prepared according to methods known to those skilled in theart [see, for example, U.S. Pat. No. 4,808,595, Journal of HeterocyclicChemistry, 8, p57, (1971), Tetrahedron Letters, p1741, (1977)], oranalogous methods thereto. Pyrrolopyridines, any one of Z¹, Z² or Z³ isa nitrogen atom in the formula (IV), can be prepared according tomethods known to those skilled in the art [see, for example, Journal ofHeterocyclic Chemistry, 29, p359, (1992)], or analogous methods thereto.

Among the compounds represented by the formula (VI),pyrrolo[3,2-c]pyridines, in which Z¹ is a nitrogen atom, can be preparedaccording to methods known to those skilled in the art [see, forexample, Journal of Chemical Research. Synopses, 1, p4, (1986) orliteratures mentioned therein], or analogous methods thereto.

Compound (VI) shown in Process 1 can be prepared according to Process Awherein compound (II) is condensed with compound (III) with heating(first step) and the resultant compound (VII) is reduced (second step),or Process B wherein compound (II) is condensed with compound (III) inwhich R⁷ is a hydrogen atom with heating, or Process C wherein compound(IV) is subjected to oxidation (first step) and then the resultantcompound (V) is subjected to amination (second step).

Process A

(1) First step:

Of the compounds represented by the formula (III), suitable R⁷ mayinclude amino group, methyl group substituted by phenyl which has 1-3straight or branched alkyl or alkoxy groups having 1 to 4 carbonatom(s), or benzyl group.

The reaction of compound (II) with compound (III) is convenientlycarried out in an organic solvent, if neccessary, such as alcohols [e.g.2-methoxyethanol, etc.], ethers [e.g. tetrahydrofuran, diethyl ether,etc.], aromatic hydrocarbons [e.g. benzene, toluene, xylene, etc.],organic amides [e.g. N,N-dimethylformamide, etc.] or other solventswhich do not adversely affect the reaction. Preferably, this reaction iscarried out without a solvent and at high temperature.

(2) Second step:

The reduction in this step may include hydrogenolysis in the presence ofcatalyst [e.g. acids such as hydrochloric acid, sulfuric acid, Lewisacid and the like, Raney nickel, palladium-carbon, platinum oxide,etc.].

The reaction is carried out in a solvent such as organic nitrites [e.g.acetonitrile, etc.], acids [e.g. acetic acid, trifluoroacetic acid,etc.], alcohols [e.g. methanol, ethanol, etc.], ethers [e.g.tetrahydrofuran, diethyl ether, etc.], aromatic hydrocarbons [e.g.benzene, toluene, xylene, etc.], organic amides [e.g.N,N-dimethylformamide, etc.], any other solvents which do not adverselyaffect the reaction, or a mixture thereof.

The reaction temperature is not critical and the reaction is usuallycarried out with cooling or heating.

The reaction is completed in 5 minutes to 24 hours.

Process B

The reaction is usually carried out in ammonium hydroxide or a solutionof ammonia in alcohol [e.g. methanol, ethanol, etc.] in a sealedreaction tube.

The reaction temperature is not critical, and the reaction is carriedout

The reaction is completed in 2 to 72 hours.

Process C

(1) First step:

The oxidation in this step may include oxidation by peroxide [e.g.inorganic peroxides such as hydrogen peroxide and the like, organicperoxides such as 3-chloroperbenzoic acid, alkyl hydroperoxide,peracetic acid and the like].

The reaction is carried out in a solvent such as organic amides [e.g.N,N-dimethylformamide, etc.], alcohols [e.g. methanol, ethanol, etc.],ethers [e.g. tetrahydrofuran, diethyl ether, dioxane, etc.],hydrocarbons [e.g. benzene, toluene, xylene, hexane, etc.], organicnitriles [e.g. acetonitrile, etc.], acids [e.g. hydrochloric acid,sulfuric acid, acetic acid, etc.], water, any other solvents which donot adversely affect the reaction, or a mixture thereof.

The reaction temperature is not critical, and the reaction is usuallycarried out with cooling or heating.

The reaction is completed. in 5 minutes to 24 hours.

(2) Second step

The amination applied to this reaction may include the reaction with anaminating agent [e.g. ethanolamine, ammonia, etc.] in the presence of anacylating agent [e.g. p-toluenesulfonyl chloride, methanesulfonylchloride, acetyl chloride, etc.].

The reaction is carried out in a solvent such as alcohols [e.g.methanol, ethanol, etc.], ethers [e.g. tetrahydrofuran, diethyl ether,dioxane, etc.], aromatic hydrocarbons [e.g. benzene, toluene, xylene,etc.], halogenated hydrocarbons [e.g. dichloromethane, chloroform,etc.], cyclic organic bases [e.g. pyridine, picoline, etc.], water, anyother solvents which do not adversely affect the reaction, or a mixturethereof.

The reaction temperature is not critical, and the reaction is usuallycarried out with cooling or heating.

The reaction is completed in 30 minutes to 48 hours. ##STR8## whereinring A, ring B, R¹, R⁴, R⁵, k, m and n are as defined above; X' is ahalogen atom.

Aminoisoquinolines, represented by the formula (VIII) in which ring B isbenzene ring, can be prepared according to procedures known to thoseskilled in the art [e.g. Chemical and Pharmaceutical Bulletin, 5, p606,(1957); Heterocycles, 38, p375, (1994); European Patent PublicationNo.143001], or analogous methods thereto. Among compounds of the formula(VIII), the compounds wherein ring B is thiophene, furan or pyrrolering, may be represented by the formula (VI), and processes forpreparing the same have been shown in aforementioned Process 1.2-Halogenoethanones represented by the formula (IX) can be preparedaccording to procedures known to those skilled in the art [e.g. JapanesePatent Publication (Kokai) No.152677/86; Journal of Medicinal Chemistry,37, p57, (1994)], or analogous methods thereto.

Compound (X) or a salt thereof can be prepared by reacting Compound(VIII) or a salt thereof with Compound (IX).

The reaction is conveniently carried out in a solvent such as alcohols[e.g. methanol, ethanol, etc.], ethers [e.g. tetrahydrofuran, diethylether, etc.], aromatic hydrocarbons [e.g. benzene, toluene, xylene,etc.], halogenated hydrocarbons [e.g. dichloromethane, chloroform,etc.], organic amides [e.g. N,N-dimethylformamide, etc.] or any othersolvents which do not adversely affect the reaction.

The reaction may be preferably carried out in the presence of aninorganic base or an organic base, such as an alkali metal hydroxide[e.g. sodium hydroxide, potassium hydroxide, etc.], an alkali metalcarbonate [e.g. sodium carbonate, potassium carbonate, etc.], an alkalimetal bicarbonate [e.g. sodium bicarbonate, potassium bicarbonate,etc.], trialkylamine [e.g. trimethylamine, triethylamine, etc.],pyridine or lutidine, or the like.

The reaction temperature is not critical, and the reaction is usuallycarried out at room temperature or with heating.

The reaction is completed in 30 minutes to 24 hours.

The compounds represented by the formula (X) may also be prepared bychange of partial structure of Compound (X) having suitablesubstituent(s) by means of a suitable means. For example, the aimedcompound can be obtained in accordance with the following reactions: byreplacing halogen such as chlorine, bromine, and the like with nitrile[see Shin jikken kagaku kouza; Maruzene company: Japan, 14, p1437], orby cross-coupling to convert halogen such as chlorine, bromine and thelike into alkyl group such as methyl, ethyl and the like or aryl groupsuch as phenyl, naphthyl, and the like [Synthesis, p317, (1985)], orhydrolysis of nitrile to carboxylic acid and its derivative [OrganicSyntheses, 2, p588, (1943)], or conversion of nitrile into acyl group byusing an organic metal reagent [Journal of Chemical Society, p4566,(1965)], or protection and deprotection of hydroxy or amino group[W.Greene, "Protective Groups in Organic Synthesis"], or reduction ofnitro group into amino group, or reduction of carboxylic acid or itsderivative into hydroxymethyl group, or alkylation of hydroxy or aminogroup, or conversion of amino group into alkylthio or arylthio group viadiazonium salt [Journal of the American Chemical Society, 82, p2872,(1960)].

Compound (Ia) or a salt thereof can be prepared by subjecting compound(X) or a salt thereof to nitrosation (first step) and then subjectingthe resultant compound to reduction (second step).

(1) First step:

Suitable nitrosating agents to be used in this reaction may includealkali metal nitrite salt [e.g. sodium nitrite, potassium nitrite,etc.], or nitrite ester [e.g. t-butyl nitrite, pentyl nitrite, isopentylnitrite, etc.] and the like.

The reaction is carried out in a solvent such as organic amides [e.g.N,N-dimethylformamide, etc.], alcohols [e.g. methanol, ethanol, etc.],ethers [e.g. tetrahydrofuran, diethyl ether, dioxane, etc.],hydrocarbons [e.g. benzene, toluene, xylene, hexane, etc.], organicnitrites [e.g. acetonitrile, etc.], acids [e.g. hydrochloric acid,sulfuric acid, acetic acid, etc.], water, any other solvents which donot adversely affect the reaction, or a mixture thereof.

The reaction temperature is not critical, and the reaction is usuallycarried out with cooling or heating.

The reaction is completed in 5 minutes to 6 hours.

(2) Second step:

The reduction applied to this reaction may include catalytic reductionin the presence of catalyst [e.g. palladium-carbon, platinum oxide,etc.] or reductions using a combination of a metal [e.g. titanium, iron,zinc, etc.] with an inorganic or organic acid such as hydrochloric acid,acetic acid, propionic acid and the like.

The reaction is carried out in a solvent such as organic amides [e.g.N,N-dimethylformamide, etc.], alcohols [e.g. methanol, ethanol, etc.],ethers [e.g. tetrahydrofuran, diethyl ether, dioxane, etc.],hydrocarbons [e.g. benzene, toluene, xylene, hexane, etc.], organicnitrites [e.g. acetonitrile, etc.], acids [e.g. hydrochloric acid,sulfuric acid, acetic acid, etc.], water, any other solvents which donot adversely affect the reaction, or a mixture thereof.

The reaction temperature is not critical, and the reaction is usuallycarried out with cooling or heating.

The reaction is completed in 5 minutes to 24 hours. ##STR9## whereinring A, ring B, R¹, R⁴, R⁵, k, m and n are as defined above; X' is ahalogen atom.

3,4-Dihydroisoquinolines represented by the formula (XI) in which ring Bis benzene ring, can be prepared according to procedures known to thoseskilled in the art [e.g. Japanese Patent Publication (Kokai)No.213870/93 or literatures cited therein], or analogous methodsthereto. Compounds represented by the formula (XI) wherein ring B isthiophene, furan or pyrrole ring, can be prepared according toprocedures known to those skilled in the art [e.g. Journal of MedicinalChemistry, 31, p641, (1988); Journal of Chemical Research Synopses, 1,p4, (1986), or literautures cited therein], or analogous methodsthereto.

5,6-Dihydroimidazopyridines represented by the formula (XII) can beprepared by reacting compound (XI) with compound (IX) (first step) andthen subjecting the resultant compound to react with an ammonium salt(second step).

(1) First step:

The reaction is carried out in a solvent such as ethers [e.g.tetrahydrofuran, diethyl ether, dioxane, etc.], hydrocarbons [e.g.benzene, toluene, xylene, hexane, etc.], halogenated hydrocarbons [e.g.dichloromethane, chloroform, etc.], organic amides [e.g.N,N-dimethylformamide, etc.] or any other solvents which do notadversely affect the reaction.

The reaction temperature is not critical, and the reaction is usuallycarried out at room temperature or with heating.

The reaction is completed in 30 minutes to 24 hours.

(2) Second step:

Suitable ammonium salts to be used in this reaction include inorganicammonium salts [e.g. ammonium carbonate, ammonium sulfate, etc.] ororganic ammonium salts [e.g. ammonium formate, ammonium acetate, etc.].

The reaction is carried out in a solvent such as organic amides [e.g.N,N-dimnethylformamide, etc.], alcohols [e.g. methanol, ethanol, etc.],ethers [e.g. tetrahydrofuran, diethyl ether, dioxane, etc.],hydrocarbons [e.g. benzene, toluene, xylene, hexane, etc.], organicnitrites [e.g. acetonitrile, etc.], acids [e.g. hydrochloric acid,sulfuric acid, acetic acid, etc.], water or any other solvents which donot adversely affect the reaction.

The reaction temperature is not critical, and the reaction is usuallycarried out at room temperature or with heating.

The reaction is completed in 30 minutes to 24 hours.

The compounds represented by the formula (XII) can also be prepared byconversion of partial structure of the compounds (XII) having suitablesubstituent(s) by using the means exemplified above.

Compound (Ib) or a salt thereof in Process 3 can be prepared fromcompound (XII) in a similar manner to the method the compound (Ia) or asalt thereof from the compound (X) or a salt thereof aforementioned inProcess 2.

The compound (X) or a salt thereof in Process 3 can also be prepared bysubjecting compound (XII) or a salt thereof to oxidation.

The oxidation applied to this reaction may include dehydrogenation inthe presence of catalyst [e.g. platinum, palladium-carbon, precipitatedalumina-chromium oxide, copper, nickel, etc.].

The reaction solvent may include, for example, diphenylether,diphenylmethane, benzene, toluene, naphthalene, tetralin, decalin, andthe like. The reaction can also be carried out without solvent.

High reaction temperature is required although it is not critical, andthe reaction is usually carried out with heating.

The reaction is completed in 30 minutes to 24 hours.

Compound (Ib) or a salt thereof can also be prepared by subjectingCompound (Ia) or a salt thereof to reduction.

The reduction applied to this reaction may include catalytic reductionin the presence of catalyst [e.g. palladium-carbon, platinum oxide,etc.].

The reaction is carried out in a solvent such as alcohols [e.g.methanol, ethanol, etc.], ethers [e.g. tetrahydrofuran, diethyl ether,dioxane, etc.], aromatic hydrocarbons [e.g. benzene, toluene, xylene,etc.], organic amides [e.g. N,N-dimethylformamide, etc.] or any othersolvents which do not adversely affect the reaction.

The reaction temperature is not critical, and the reaction is preferablycarried out at ambient temperature or at the boiling point of thesolvent used.

The reaction is completed in 30 minutes to 72 hours. ##STR10## whereinring A, ring B, R¹, R⁴, R⁵, k, m and n are as defined above; R⁸ ishydrogen atom, lower alkoxy group, alkenyl group, or lower alkyl groupwhich may have substituent(s) selected from halogen atom, hydroxy group,lower alkoxy group, alkylthio group, alkylsulfinyl group, alkoxycarbonylgroup, carbamoyl group, alkyl amino group, or aryl group; R⁹ and R¹⁰ maybe same or different and each represent hydrogen atom, lower alkoxygroup, alkenyl group or lower alkyl group which may have substituent(s)selected from halogen atom, alkoxycarbonyl group, carbamoyl group,alkylamino group or aryl group.

Compound (Id) or a salt thereof can be prepared by subjecting compound(Ic) or a salt thereof to acylation.

The acylating agent to be used in this reaction may include desiredcarboxylic acids, carboxylic anhydrides, halogenated acyls or acombination of any one of those compounds with a suitable condensingagent.

The reaction is carried out in a solvent such as cyclic organic bases[e.g. pyridine, etc.], alcohols [e.g. methanol, ethanol, etc.], ethers[e.g. tetrahydrofuran, diethyl ether, dioxane, etc.], hydrocarbons [e.g.benzene, toluene, xylene, hexane, etc.], halogenated hydrocarbons [e.g.dichloromethane, chloroform, etc.], organic amides [e.g.N,N-dimethylformamide, etc.] or any other solvents which do notadversely affect the reaction.

The reaction temperature is not critical, and the reaction is usuallycarried out with cooling or heating.

The reaction is completed in 5 minutes to 6 hours.

Compounds (If), (Ig) and (Ie) or salts thereof can be prepared bysubjecting the compounds (Ic), (If) and (Id) or salts thereof toalkylation.

The alkylating agent to be used in this reaction may include desiredhalogenated alkyls, halogenated arylalkyls or halogenated alkenyls andthe like.

The reaction is usually carried out in the presence of a base.

Suitable bases may include inorganic bases such as alkali metal hydrides[e.g. sodium hydride, potassium hydride, etc.], alkali metal hydroxides[e.g. sodium hydroxide, potassium hydroxide, etc.], alkaline earth metalhydroxides [e.g. magnesium hydroxide, calcium hydroxide, etc.], alkalimetal carbonates [e.g. sodium carbonate, potassium carbonate, etc.],alkaline earth metal carbonates [e.g. magnesium carbonate, calciumcarbonate, etc.], alkali metal bicarbonates [e.g. sodium bicarbonate,potassium bicarbonate, etc.], alkaline earth metal phosphates [e.g.magnesium phosphate, calcium phosphate, etc.], alkali metal acetates[e.g. sodium acetate, potassium acetate, etc.], or the like, and organicbases such as trialkylamines [e.g. trimethylamine, triethylamine, etc.],pyridine, picoline, N-methylmorpholine, N-methylpyrrolidine, or thelike.

The reaction is carried out in a solvent such as alcohols [e.g.methanol, ethanol, etc.], ethers [e.g. tetrahydrofuran, diethyl ether,dioxane, etc.], hydrocarbons [e.g. benzene, toluene, xylene, hexane,etc.], organic amides [e.g. N,N-dimethylformamide, etc.] or any othersolvents which do not adversely affect the reaction.

The reaction temperature is not critical, and the reaction is preferablycarried out at ambient temperature or at the boiling point of thesolvent used.

The reaction is completed in 5 minutes to 24 hours.

Compounds (If) and (Ig) or salts thereof can also be prepared bysubjecting compounds (Id) and (Ie) or salts thereof to reduction.

Suitable reducing agent to be used in this reaction may include lithiumaluminium hydride and the like.

This reaction is usually carried out in a solvent such as ethers [e.g.tetrahydrofuran, diethyl ether, dioxane, etc.], hydrocarbons [e.g.benzene, toluene, xylene, hexane, etc.] or any other solvents which donot adversely affect the reaction.

The reaction temperature is not critical, and the reaction is usuallycarried out with cooling or heating.

The reaction is completed in 5 minutes to 24 hours. ##STR11## whereinring A, ring B, R¹, R⁴, R⁵, R⁸, R¹⁰, k, m and n are as defined above.

Compound (Ih) or a salt thereof can be prepared by subjecting compound(Ic) or a salt thereof and a desired aldehyde to dehydration.

This reaction is usually carried out in a solvent such as alcohols [e.g.methanol, ethanol, etc.], ethers [e.g. tetrahydrofuran, diethyl ether,dioxane, etc.], aromatic hydrocarbons [e.g. benzene, toluene, xylene,etc.], halogenated hydrocarbons [e.g. dichloromethane, chloroform, etc.]or any other solvents which do not adversely affect the reaction, orwithout solvent.

As a catalyst, there may be used an inorganic base such as alkali metalhydroxide [e.g. sodium hydroxide, potassium hydroxide, etc.], aninorganic acid [e.g. hydrochloric acid, sulfuric acid, etc.] or Lewisacid [e.g. toluenesulfonic acid, zinc chloride, boron trifluoride,etc.].

The reaction temperature is not critical, and the reaction is usuallycarried out with cooling or heating.

The reaction is completed in 5 minutes to 24 hours.

Compound (If) or a salt thereof can also be prepared by subjectingcompound (Ih) or a salt thereof to reduction.

Reductions applied to this reaction may include a reduction using metalhydride complex [e.g. sodium borohydride, etc.] and catalytic reductionin the presence of catalyst [e.g. palladium-carbon, platinum oxide,etc.].

This reaction is carried out in a solvent such as alcohols [e.g.methanol, ethanol, etc.], ethers [e.g. tetrahydrofuran, diethyl ether,dioxane, etc.], aromatic hydrocarbons [e.g. benzene, toluene, xylene,etc.], organic amides [e.g. N,N-dimethylformamide, etc.] or any othersolvents which do not adversely affect the reaction.

The reaction temperature is not critical, and the reaction is preferablycarried out at ambient temperature or at the boiling point of thesolvent used.

The reaction is completed in 5 minutes to 24 hours.

Suitable salts of compounds (Ia)-(Ih), (X) and (XII) are acid additionsalts as exemplified in compounds (I).

The compounds represented by the formula (I) can also be prepared. byconversion of partial structure of compounds (I) having suitablesubstituent(s) using means as partly exemplified above.

The intermediates and aimed compounds obtained in the above processescan be isolated and purified using purification processes convenientlyused in synthetic organic chemistry, for example, filtration,extraction, washing, concentration, drying, recrystallization, variouschromatographies and the like. Intermediates can also be used insubsequent reactions without further purification.

When salts of compounds (I) are desirous to obtain and compound (I) isproduced in the form of a salt, it may be suitably purified. Whencompound (I) is produced in the form of a free base, a salt can beobtained by the addition of an acid to a solution or suspension ofcompound (I) in a suitable organic solvent. Compounds (I) andpharmaceutically acceptable salts thereof can also exist as adducts withwater or the solvent used. These adducts are included in this invention.

The compounds of the invention represented by the general formula (I)are shown in Table 1 and Table 2. The compound numbers will be referredto in the description hereinafter. The compounds represented by theformula (I-1) are shown in Table 1 and the compounds represented by theformula (I-2) are shown in Table 2. For reader's convenience, chemicalformulae I-1) and I-2) in which position numbers are indicated areprovided below. ##STR12##

In Table 1 and Table 2, substituents are sometimes indicated usingabbreviations, which are as follows:

Me methyl group

Et ethyl group

Pr n-propyl group

i-Pr isopropyl group

Pip piperidino group

Mor morpholino group

Suc succinimide group

Ph phenyl group

Bu n-butyl group

Pen n-pentyl group

i-Pen isopentyl group

c-Pen cyclopentyl group

Hex n-hexyl group

Ac acetyl group

Fu furyl group

Pyr pyrrolyl group

Th thienyl group

Naph naphthyl group

Bzfu benzo[b]furyl group

In Table 1 and Table 2, the number in parentheses means the positionwhere ring A binds to the 2-position, and the number and substitution inbrackets means where the substituent(s) R¹ locates on ring A. Inaddition, the number in parentheses indicates the position on the arylgroup at which it binds to other group, and the number and substitutionin brackets indicates the position and nature of the substitution on thearyl group. Several examples are given below. ##STR13##

In column "5-6"of Table 1 and Table 2, "DB" means that the dotted line,together with the solid line, represents a double bond between the 5-and 6-positions in the the formula (I-1) or I-2), while "SB" means thatthe bond represents a single bond. ##STR14##

                                      TABLE 1                                     __________________________________________________________________________    Examples of the compounds according to the invention represented              by the formula (I-1).                                                         Compound  No                                                                                   NR.sup.2 R.sup.3                                                                         R.sup.4, R.sup.5                                                                       5-6                                      __________________________________________________________________________    1     [2-F]Ph    NH.sub.2   --       DB                                       2     [2-Cl]Ph   NH.sub.2   --       DB                                       3     [2-Me]Ph   NH.sub.2   --       DB                                       4     [2-Me]Ph   NH.sub.2   9-F      DB                                       5     [2-Me]Ph   NH.sub.2   7-Cl     DB                                       6     [2-Me]Ph   NH.sub.2   9-Cl     DB                                       7     [2-Me]Ph   NH.sub.2   10-Cl    DB                                       8     [2-Me]Ph   NH.sub.2   7-Br     DB                                       9     [2-Me]Ph   NH.sub.2   5-Me     DB                                       10    [2-Me]Ph   NH.sub.2   9-Me     DB                                       11    [2-Me]Ph   NH.sub.2   5-Et     DB                                       12    [2-Me]Ph   NH.sub.2   5-Pr     DB                                       13    [2-Me]Ph   NH.sub.2   7-Pr     DB                                       14    [2-Me]Ph   NH.sub.2   5-i-Pr   DB                                       15    [2-Me]Ph   NH.sub.2   6-i-Pen  DB                                       16    [2-Me]Ph   NH.sub.2   6-CH.sub.2 OMe                                                                         DB                                       17    [2-Me]Ph   NH.sub.2   6-CH.sub.2 OPh                                                                         DB                                       18    [2-Me]Ph   NH.sub.2   7-CH.sub.2 OH                                                                          DB                                       19    [2-Me]Ph   NH.sub.2   9-CH(OH)Me                                                                             DB                                       20    [2-Me]Ph   NH.sub.2   9-Ph     DB                                       21    [2-Me]Ph   NH.sub.2   6-[4-OMe]Ph                                                                            DB                                       22    [2-Me]Ph   NH.sub.2   9-OH     DB                                       23    [2-Me]Ph   NH.sub.2   5-OMe    DB                                       24    [2-Me]Ph   NH.sub.2   6-OMe    DB                                       25    [2-Me]Ph   NH.sub.2   7-OMe    DB                                       26    [2-Me]Ph   NH.sub.2   9-OMe    DB                                       27    [2-Me]Ph   NH.sub.2   6-OEt    DB                                       28    [2-Me]Ph   NH.sub.2   9-OEt    DB                                       29    [2-Me]Ph   NH.sub.2   9-OPr    DB                                       30    [2-Me]Ph   NH.sub.2   9-Oi-Pr  DB                                       31    [2-Me]Ph   NH.sub.2   9-OBu    DB                                       32    [2-Me]Ph   NH.sub.2   7,9-(OMe).sub.2                                                                        DB                                       33    [2-Me]Ph   NH.sub.2   8,9-(OMe).sub.2                                                                        DB                                       34    [2-Me]Ph   NH.sub.2   9,10-(OMe).sub.2                                                                       DB                                       35    [2-Me]Ph   NH.sub.2   9-OCH.sub.2 CO.sub.2 Et                                                                DB                                       36    [2-Me]Ph   NH.sub.2   9-OCH.sub.2 CH.sub.2 OH                                                                DB                                       37    [2-Me]Ph   NH.sub.2   9-OCH.sub.2 CH.sub.2 OMe                                                               DB                                       38    [2-Me]Ph   NH.sub.2   6-OCH.sub.2 Ph                                                                         DB                                       39    [2-Me]Ph   NH.sub.2   7-OCH.sub.2 Ph                                                                         DB                                       40    [2-Me]Ph   NH.sub.2   9-OCH.sub.2 Ph                                                                         DB                                       41    [2-Me]Ph   NH.sub.2   9-OAc    DB                                       42    [2-Me]Ph   NH.sub.2   9-OCOPr  DB                                       43    [2-Me]Ph   NH.sub.2   9-OCO-i-Pr                                                                             DB                                       44    [2-Me]Ph   NH.sub.2   9-OCONMe.sub.2                                                                         DB                                       45    [2-Me]Ph   NH.sub.2   7-SCH.sub.2 Ph                                                                         DB                                       46    [2-Me]Ph   NH.sub.2   7-SMe    DB                                       47    [2-Me]Ph   NH.sub.2   6-Ac     DB                                       48    [2-Me]Ph   NH.sub.2   7-CO-[4-OMe]Ph                                                                         DB                                       49    [2-Me]Ph   NH.sub.2   7-CO.sub.2 H                                                                           DB                                       50    [2-Me]Ph   NH.sub.2   6-CO.sub.2 Me                                                                          DB                                       51    [2-Me]Ph   NH.sub.2   7-CO.sub.2 Me                                                                          DB                                       52    [2-Me]Ph   NH.sub.2   7-CN     DB                                       53    [2-Me]Ph   NH.sub.2   9-CN     DB                                       54    [2-Me]Ph   NH.sub.2   7-N(Et).sub.2                                                                          DB                                       55    [2-Me]Ph   NH.sub.2   9-OMe,10-Cl                                                                            DB                                       56    [2-Me]Ph   NH.sub.2   5-Me,9-OMe                                                                             DB                                       57    [3-Me]Ph   NH.sub.2   --       DB                                       58    [4-Me]Ph   NH.sub.2   --       DB                                       59    [2-Et]Ph   NH.sub.2   --       DB                                       60    [2-CF.sub.3 ]Ph                                                                          NH.sub.2   --       DB                                       61    [2-OMe]Ph  NH.sub.2   --       DB                                       62    [2,4-Me.sub.2 ]Ph                                                                        NH.sub.2   --       DB                                       63    [2-Me,4-Et]Ph                                                                            NH.sub.2   --       DB                                       64    [2-Me,4-F]Ph                                                                             NH.sub.2   5-Me     DB                                       65    [2-Me,5-F]Ph                                                                             NH.sub.2   6-OMe    DB                                       66    [2-Me,4-Cl]Ph                                                                            NH.sub.2   --       DB                                       67    [2-Me,5-Cl]Ph                                                                            NH.sub.2   10-Cl    DB                                       68    [2-Me,4-OH]Ph                                                                            NH.sub.2   --       DB                                       69    [2-Me,4-OMe]Ph                                                                           NH.sub.2   --       DB                                       70    [2-Me,4-OAc]Ph                                                                           NH.sub.2   --       DB                                       71    [2,4,6-Me.sub.3 ]Ph                                                                      NH.sub.2   --       DB                                       72    [2-Me,4-OMe,5-Br]Ph                                                                      NH.sub.2   --       DB                                       73    [3-Me]Th(2)                                                                              NH.sub.2   --       DB                                       74    [3-Me]Th(2)                                                                              NH.sub.2   6-OMe    DB                                       75    [3-Me]Th(2)                                                                              NH.sub.2   9-OMe    DB                                       76    [4-Me]Th(2)                                                                              NH.sub.2   --       DB                                       77    [3-Et]Th(2)                                                                              NH.sub.2   --       DB                                       78    [2-Me]Th(3)                                                                              NH.sub.2   --       DB                                       79    [2-Me]Th(3)                                                                              NH.sub.2   5-Me     DB                                       80    [2-Me]Th(3)                                                                              NH.sub.2   5-OMe    DB                                       81    [4-Me]Th(3)                                                                              NH.sub.2   --       DB                                       82    [2-Et]Th(3)                                                                              NH.sub.2   --       DB                                       83    [2,5-Me.sub.2 ]Th(3)                                                                     NH.sub.2   --       DB                                       84    [2,5-Cl.sub.2, 4-Me]Th(3)                                                                NH.sub.2   --       DB                                       85    [2-Cl,3-Me]Th(4)                                                                         NH.sub.2   --       DB                                       86    [2-Cl,3-Me]Th(4)                                                                         NH.sub.2   7-Br     DB                                       87    [2-Cl,3-Me]Th(4)                                                                         NH.sub.2   5-Me     DB                                       88    [3-Me]Fu(2)                                                                              NH.sub.2   --       DB                                       89    [2-Me]Fu(3)                                                                              NH.sub.2   --       DB                                       90    [2-Me]Fu(3)                                                                              NH.sub.2   5-Me     DB                                       91    [2,5-Me.sub.2 ]Fu(3)                                                                     NH.sub.2   --       DB                                       92    [2,5-Me.sub.2 ]Fu(3)                                                                     NH.sub.2   5-OMe    DB                                       93    [2,5-Me.sub.2 ]Fu(3)                                                                     NH.sub.2   9-OMe    DB                                       94    [1-Me]Pyr(2)                                                                             NH.sub.2   --       DB                                       95    [1-Et]Pyr(2)                                                                             NH.sub.2   --       DB                                       96    [2-Me]Ph   NH.sub.2   --       SB                                       97    [2-Me]Ph   NH.sub.2   9-F      SB                                       98    [2-Me]Ph   NH.sub.2   8-Cl     SB                                       99    [2-Me]Ph   NH.sub.2   9-Br     SB                                       100   [2-Me]Ph   NH.sub.2   5-Me     SB                                       101   [2-Me]Ph   NH.sub.2   7-Me     SB                                       102   [2-Me]Ph   NH.sub.2   9-Me     SB                                       103   [2-Me]Ph   NH.sub.2   9-OMe    SB                                       104   [2-Me]Ph   NH.sub.2   5,5-Me.sub.2                                                                           SB                                       105   [2-Me]Ph   NH.sub.2   6,7-Me.sub.2                                                                           SB                                       106   [2-Me]Ph   NH.sub.2   5-Me,9-OMe                                                                             SB                                       107   [2-Me,4-OH]Ph                                                                            NH.sub.2   --       SB                                       108   [2-Me,4-OH, 5-Br]Ph                                                                      NH.sub.2   --       SB                                       109   [2-Me]Th(3)                                                                              NH.sub.2   --       SB                                       110   [2,5-Me.sub.2 ]Th(3)                                                                     NH.sub.2   --       SB                                       111   [2-F]Ph    NH(Ac)     --       DB                                       112   [2-Me]Ph   NH(Ac)     --       DB                                       113   [2-Me]Ph   NH(Ac)     6-i-Pen  DB                                       114   [2-Me]Ph   NH(Ac)     7-Pr     DB                                       115   [2-Me]Ph   NH(Ac)     6-OMe    DB                                       116   [2-Me]Ph   NH(Ac)     9-OMe    DB                                       117   [2-Me]Ph   NH(Ac)     7,9-(OMe).sub.2                                                                        DB                                       118   [3-Me]Ph   NH(Ac)     --       DB                                       119   [4-Me]Ph   NH(Ac)     --       DB                                       120   [2-Et]Ph   NH(Ac)     --       DB                                       121   [3-Me]Th(2)                                                                              NH(Ac)     --       DB                                       122   [3-Et]Th(2)                                                                              NH(Ac)     --       DB                                       123   [2-Cl,3-Me]Th(4)                                                                         NH(Ac)     --       DB                                       124   [2-Me]Ph   NH(COCH.sub.2 CH.sub.2 Cl)                                                               --       DB                                       125   [2-Me]Ph   NH(COCH.sub.2 CH.sub.2 SMe)                                                              --       DB                                       126   [2-Me]Ph   NH(COCH.sub.2 CH.sub.2 COOH)                                                             --       DB                                       127   [2,4-Me.sub.2 ]Ph                                                                        NH(COCH.sub.2 CH.sub.2 COOH)                                                             --       DB                                       128   [2-Me]Ph   NH(COPen)  --       DB                                       129   [2-Me]Ph   NH(COCH═CHCO.sub.2 Me)                                                               --       DB                                       130   [2-Me]Ph   NH(CO-[3-CF.sub.3 ]Ph)                                                                   --       DB                                       131   [2-Me]Ph   NH(CO-[4-OMe]Ph)                                                                         --       DB                                       132   [2-Me]Ph   NH(CO-Th(2))                                                                             --       DB                                       133   [2-Me]Ph   NH(CO-[3-Me]Bzfu(2))                                                                     --       DB                                       134   [2-Me]Ph   N(Ac)(CH.sub.2 CO.sub.2 Et)                                                              --       DB                                       135   [3-Et]Th(2)                                                                              N(Ac)(CH.sub.2 CON(Et).sub.2)                                                            --       DB                                       136   [2-Me]Ph   N(Ac)(CH.sub.2 CH.sub.2 OMe)                                                             --       DB                                       137   [2-F]Ph    N(Ac)(Pr)  --       DB                                       138   [2-Me]Ph   N(Ac)(Pr)  --       DB                                       139   [2-Me]Ph   N(Ac)(Pr)  6-i-Pen  DB                                       140   [2-Me]Ph   N(Ac)(Pr)  6-OMe    DB                                       141   [2-Me]Ph   N(Ac)(Pr)  9-OMe    DB                                       142   [2-Me]Ph   N(Ac)(Pr)  8,9-(OMe).sub.2                                                                        DB                                       143   [3-Me]Ph   N(Ac)(Pr)  --       DB                                       144   [3-Me]Th(2)                                                                              N(Ac)(Pr)  --       DB                                       145   [2-Me]Ph   N(Ac)(i-Pr)                                                                              --       DB                                       146   [2-Me]Ph   N(Ac)(CH.sub.2 CH═CH.sub.2)                                                          --       DB                                       147   [4-Me]Ph   N(Ac)(i-Pen)                                                                             --       DB                                       148   [2-Et]Ph   N(Ac)(i-Pen)                                                                             --       DB                                       149   [2,4-Me.sub.2 ]Ph                                                                        N(Ac)(i-Pen)                                                                             --       DB                                       150   [2-Et]Ph   N(Ac)(CH.sub.2 -[4-Me]Ph)                                                                --       DB                                       151   [2-Me]Ph   N(Ac)(CH.sub.2 -[4-Me]Ph)                                                                --       DB                                       152   [2-Me]Ph   N(COCH.sub.2 CH.sub.2 SMe)(Et)                                                           --       DB                                       153   [2-Me]Ph   Suc        --       DB                                       154   [2,4-Me.sub.2 ]Ph                                                                        Suc        --       DB                                       155   [2-Me]Ph   NH(CH.sub.2 CO.sub.2 Et)                                                                 --       DB                                       156   [2-Me]Ph   NH(CH.sub.2 CO.sub.2 Pr)                                                                 --       DB                                       157   [2-Me]Ph   NH(CH.sub.2 CON(Et).sub.2)                                                               --       DB                                       158   [2-Me]Ph   NH(Et)     --       DB                                       159   [2-Me]Ph   NH(Et)     7-Cl     DB                                       160   [2-Me]Ph   NH(Et)     9-Cl     DB                                       161   [2-Me]Ph   NH(Et)     5-Me     DB                                       162   [2-Me]Ph   NH(Et)     6-i-Pen  DB                                       163   [2-Me]Ph   NH(Et)     7-Pr     DB                                       164   [2-Me]Ph   NH(Et)     6-CH.sub.2 OMe                                                                         DB                                       165   [2-Me]Ph   NH(Et)     7-OH     DB                                       166   [2-Me]Ph   NH(Et)     6-OMe    DB                                       167   [2-Me]Ph   NH(Et)     9-OMe    DB                                       168   [2-Me]Ph   NH(Et)     6-OCH.sub.2 Ph                                                                         DB                                       169   [2-Me]Ph   NH(Et)     7-OCH.sub.2 Ph                                                                         DB                                       170   [2-Me]Ph   NH(Et)     7-SMe    DB                                       171   [2-Me]Ph   NH(Et)     7-OAc    DB                                       172   [2-Me]Ph   NH(Et)     7-CO.sub.2 Me                                                                          DB                                       173   [2-Me]Ph   NH(Et)     7-CO.sub.2 Et                                                                          DB                                       174   [2-Me]Ph   NH(Et)     7-N(Et).sub.2                                                                          DB                                       175   [2-CF.sub.3 ]Ph                                                                          NH(Et)     --       DB                                       176   [3-Me]Th(2)                                                                              NH(Et)     6-OMe    DB                                       177   [3-Me]Th(2)                                                                              NH(Et)     9-OMe    DB                                       178   [3-Et]Th(2)                                                                              NH(Et)     --       DB                                       179   [2-Cl,3-Me]Th(4)                                                                         NH(Et)     --       DB                                       180   [2-Me]Ph   NH(CH.sub.2 CH.sub.2 OMe)                                                                --       DB                                       181   [2-Me]Ph   NH(Pr)     6-i-Pen  DB                                       182   [2-Me]Ph   NH(Pr)     6-OMe    DB                                       183   [2-Me]Ph   NH(Pr)     9-OMe    DB                                       184   [2-Me]Ph   NH(i-Pr)   --       DB                                       185   [2-Me]Ph   NH(CH.sub.2 CH.sub.2 CH.sub.2 SMe)                                                       --       DB                                       186   [2-Me]Ph   NH(CH.sub.2 CH.sub.2 CH.sub.2 SOMe)                                                      --       DB                                       187   [2-Me]Ph   NH(Pen)    --       DB                                       188   [2-Me]Ph   NH(i-Pen)  --       DB                                       189   [2,4-Me.sub.2 ]Ph                                                                        NH(i-Pen)  --       DB                                       190   [2-Me]Ph   NH(c-Pen)  --       DB                                       191   [2-Me]Ph   NH(Hex)    --       DB                                       192   [2-Me]Ph   NH(CH(Me)(Ph))                                                                           --       DB                                       193   [2-Me]Ph   NH(CH.sub.2 -[4-F]Ph)                                                                    --       DB                                       194   [2-Me]Ph   NH(CH.sub.2 -[4-Me]Ph)                                                                   --       DB                                       195   [2-Me]Ph   NH(CH.sub.2 -[1-Br]Naph(2))                                                              --       DB                                       196   [2-Me]Ph   NH(CH.sub.2 -[3-Me]Bzfu(2))                                                              --       DB                                       197   [2-Me]Ph   N(Me).sub.2                                                                              7-CO.sub.2 Me                                                                          DB                                       198   [2-Me]Ph   N(CH.sub.2 CON(Et).sub.2).sub.2                                                          --       DB                                       199   [2-Me]Ph   N(Et).sub.2                                                                              7-Cl     DB                                       200   [2-Me]Ph   N(Et).sub.2                                                                              7-Br     DB                                       201   [2-Cl,3-Me]Th(4)                                                                         N(Et).sub.2                                                                              --       DB                                       202   [2-Me]Ph   N(Et)(CH.sub.2 CH.sub.2 Cl)                                                              --       DB                                       203   [3-Et]Th(2)                                                                              N(Et)(CH.sub.2 CH.sub.2 N(Et).sub.2)                                                     --       DB                                       204   [2-Me]Ph   N(Et)(CH.sub.2 CH.sub.2 OH)                                                              --       DB                                       205   [2-Me]Ph   N(Et)(CH.sub.2 CH.sub.2 OMe)                                                             --       DB                                       206   [2-F]Ph    N(Et)(Pr)  --       DB                                       207   [2-Me]Ph   N(Et)(Pr)  --       DB                                       208   [2-Me]Ph   N(Et)(Pr)  6-i-Pen  DB                                       209   [2-Me]Ph   N(Et)(Pr)  9-OMe    DB                                       210   [2-Me]Ph   N(Et)(Pr)  7,9-(OMe).sub.2                                                                        DB                                       211   [3-Me]Ph   N(Et)(Pr)  --       DB                                       212   [3-Me]Th(2)                                                                              N(Et)(Pr)  --       DB                                       213   [2-Me]Ph   N(Et)(i-Pr)                                                                              --       DB                                       214   [2-Me]Ph   N(Et)(CH.sub.2 CH.sub.2 CH.sub.2 SMe)                                                    --       DB                                       215   [2,5-Me.sub.2 ]Th(3)                                                                     N(Et)(CH.sub.2 CH.sub.2 CH.sub.2 SMe)                                                    7-OCH.sub.2 Ph                                                                         DB                                       216   [2-Et]Ph   N(Et)(i-Pen)                                                                             --       DB                                       217   [2-Me]Ph   Pip        --       DB                                       218   [2-Me]Ph   Mor        --       DB                                       219   [2-Me]Ph   N(Et)(CH.sub.2 -[4-Me]Ph)                                                                --       DB                                       220   [2-Et]Ph   N(Et)(CH.sub.2 -[-4-Me]Ph)                                                               --       DB                                       221   [2-Me]Ph   NH(CH.sub.2 CH═CH.sub.2)                                                             --       DB                                       222   [2-Me]Ph   N(Et)(CH.sub.2 CH═CH.sub.2)                                                          --       DB                                       223   [2-Me]Ph   N(CH.sub.2 CH═CH.sub.2).sub.2                                                        --       DB                                       224   [2-Me]Ph   N═CHCH.sub.2 CH.sub.3                                                                --       DB                                       225   [2-Me]Ph   N═CH-[4-Me]Ph                                                                        --       DB                                       226   [2-Et]Ph   N═CH-[4-Me]Ph                                                                        --       DB                                       227   [2-Me]Fu(3)                                                                              N═CH-[4-Me]Ph                                                                        7-SCH.sub.2 Ph                                                                         DB                                       228   [2-Me]Ph   N═CH-[1-Br]NaPh(2)                                                                   --       DB                                       __________________________________________________________________________     ##STR15##

                                      TABLE 2                                     __________________________________________________________________________    Examples of the compounds according to the invention represented              by the formula (I-2).                                                         Compound  No                                                                        Z.sup.1                                                                         Z.sup.2                                                                         Z.sup.3                                                                                  NR.sup.2 R.sup.3                                                                        R.sup.4, R.sup.5                                                                       5-6                                   __________________________________________________________________________    229   S C C Ph       NH.sub.2  --       DB                                    230   S C C Ph       NH.sub.2  5-Me     DB                                    231   S C C [2-OH]Ph NH.sub.2  5-Me     DB                                    232   S C C [2-Cl]Ph NH.sub.2  --       DB                                    233   S C C [4-Cl]Ph NH.sub.2  5-Me     DB                                    234   S C C [2-Me]Ph NH.sub.2  --       DB                                    235   S C C [2-Me]Ph NH.sub.2  8-Br     DB                                    236   S C C [2-Me]Ph NH.sub.2  5-Me     DB                                    237   S C C [2-Me]Ph NH.sub.2  8-Me     DB                                    238   S C C [2-Me]Ph NH.sub.2  5-Et     DB                                    239   S C C [2-Me]Ph NH.sub.2  5,6-Me.sub.2                                                                           DB                                    240   S C C [2-Me]Ph NH.sub.2  5,8-Me.sub.2                                                                           DB                                    241   S C C [2-Me]Ph NH.sub.2  8-OMe    DB                                    242   S C C [3-Me]Ph NH.sub.2  5-Me     DB                                    243   S C C [2-Et]Ph NH.sub.2  5-Me     DB                                    244   S C C [2-CF.sub.3 ]Ph                                                                        NH.sub.2  5-Me     DB                                    245   S C C [2-OMe]Ph                                                                              NH.sub.2  5-Me     DB                                    246   S C C [4-OAc]Ph                                                                              NH.sub.2  5-Me     DB                                    247   S C C [2-Me,4-F]Ph                                                                           NH.sub.2  5-Me     DB                                    248   S C C [2-Me,4-Cl]Ph                                                                          NH.sub.2  5-Me     DB                                    249   S C C Th(2)    NH.sub.2  5-Me     DB                                    250   S C C [3-Me]Th(2)                                                                            NH.sub.2  --       DB                                    251   S C C [3-Me]Th(2)                                                                            NH.sub.2  5-Me     DB                                    252   S C C [3-Me]Th(2)                                                                            NH.sub.2  8-Me     DB                                    253   S C C Th(3)    NH.sub.2  5-Me     DB                                    254   S C C [2-Me]Th(3)                                                                            NH.sub.2  --       DB                                    255   S C C [2-Me]Th(3)                                                                            NH.sub.2  5-Me     DB                                    256   S C C [2-Me]Th(3)                                                                            NH.sub.2  8-Me     DB                                    257   S C C [2-Me]Th(3)                                                                            NH.sub.2  8-OMe    DB                                    258   S C C [2-Me]Th(3)                                                                            NH.sub.2  5,6-Me.sub.2                                                                           DB                                    259   S C C [2-Me]Th(3)                                                                            NH.sub.2  --       DB                                    260   S C C [2-Et]Th(3)                                                                            NH.sub.2  5-Me     DB                                    261   S C C [2-Me]Th(3)                                                                            NH.sub.2  5-Me     DB                                    262   S C C [2,5-Cl.sub.2 ]Th(3)                                                                   NH.sub.2  --       DB                                    263   S C C [2,5-Cl.sub.2 ]Th(3)                                                                   NH.sub.2  5-Me     DB                                    264   S C C [2,5-Me.sub.2 ]Th(3)                                                                   NH.sub.2  --       DB                                    265   S C C [2,5-Me.sub.2 ]Th(3)                                                                   NH.sub.2  5-Me     DB                                    266   S C C [2-Cl,3-Me]Th(4)                                                                       NH.sub.2  5-Me     DB                                    267   S C C Fu(2)    NH.sub.2  5-Me     DB                                    268   S C C Fu(3)    NH.sub.2  5-Me     DB                                    269   S C C [2-Me]Fu(3)                                                                            NH.sub.2  --       DB                                    270   S C C [2-OMe]Fu(3)                                                                           NH.sub.2  --       DB                                    271   S C C [2,5-Me.sub.2 ]Fu(3)                                                                   NH.sub.2  --       DB                                    272   S C C [2,5-Me.sub.2 ]Fu(3)                                                                   NH.sub.2  8-Br     DB                                    273   S C C [2,5-Me.sub.2 ]Fu(3)                                                                   NH.sub.2  5-Me     DB                                    274   S C C [2,5-Me.sub.2 ]Fu(3)                                                                   NH.sub.2  8-Me     DB                                    275   S C C [1-Me]Pyr(2)                                                                           NH.sub.2  --       DB                                    276   O C C [2-Me]Ph NH.sub.2  --       DB                                    277   O C C [2-Me]Ph NH.sub.2  5-Me     DB                                    278   O C C [2-CF.sub.3 ]Ph                                                                        NH.sub.2                                                 279   O C C [2-CF.sub.3 ]Ph                                                                        NH.sub.2  5-Me     DB                                    280   O C C [2-Me]Th(3)                                                                            NH.sub.2  --       DB                                    281   O C C [2-Me]Th(3)                                                                            NH.sub.2  5-Me     DB                                    282   O C C [2-Et]Th(3)                                                                            NH.sub.2  5-Me     DB                                    283   O C C [2-OMe]Th(3)                                                                           NH.sub.2  5-Me     DB                                    284   O C C [2,5-Cl.sub.2 ]Th(3)                                                                   NH.sub.2  --       DB                                    285   O C C [2-Me,5-Br]Th(3)                                                                       NH.sub.2  --       DB                                    286   O C C [2,5-Me.sub.2 ]Th(3)                                                                   NH.sub.2  --       DB                                    287   O C C [3-Me]Fu(2)                                                                            NH.sub.2  --       DB                                    288   O C C [2,5-Me.sub.2 ]Fu(3)                                                                   NH.sub.2  --       DB                                    289   O C C [1-Me]Pyr(3)                                                                           NH.sub.2  --       DB                                    290   N C C [2-Me]Ph NH.sub.2  --       DB                                    291   N C C [2-Me]Ph NH.sub.2  7-Me     DB                                    292   N C C [2-Me]Ph NH.sub.2  7-CH.sub.2 Ph                                                                          DB                                    293   N C C [2-Me]Ph NH.sub.2  7-CH.sub.2 -[4-Cl]Ph                                                                   DB                                    294   N C C [2-Me]Ph NH.sub.2  7-CH.sub.2 -[4-OMe]Ph                                                                  DB                                    295   N C C [2-Me]Ph NH.sub.2  5,7-Me.sub.2                                                                           DB                                    296   N C C [2-Me]Th(3)                                                                            NH.sub.2  7-Me     DB                                    297   N C C [2-Et]Th(3)                                                                            NH.sub.2  7-CH.sub.2 Ph                                                                          DB                                    298   N C C [2-Me]Th(3)                                                                            NH.sub.2  5,7-Me.sub.2                                                                           DB                                    299   N C C [2-Cl,3-Me]Th(4)                                                                       NH.sub.2  7-Me     DB                                    300   N C C [2-Cl]Fu(3)                                                                            NH.sub.2  7-CH.sub.2 Ph                                                                          DB                                    301   N C C [2,5-Me.sub.2 ]Fu(3)                                                                   NH.sub.2  7-Me     DB                                    302   N C C [1-Me]Pyr(2)                                                                           NH.sub.2  7-Me     DB                                    303   C S C [2-Me]Ph NH.sub.2  5-Me     DB                                    304   C S C [3-Me]Th(2)                                                                            NH.sub.2  --       DB                                    305   C S C [2-Me]Th(3)                                                                            NH.sub.2  5-Me     DB                                    306   C S C [1-Me)Pyr(2)                                                                           NH.sub.2  --       DB                                    307   C O C [2-Me]Ph NH.sub.2  --       DB                                    308   C O C [2-Me]Th(3)                                                                            NH.sub.2  --       DB                                    309   C C S [2-Cl]Ph NH.sub.2  5-Me     DB                                    310   C C S [2-Me]Ph NH.sub.2  --       DB                                    311   C C S [2-Me]Ph NH.sub.2  5-Me     DB                                    312   C C S [2-Me]Ph NH.sub.2  8-Me     DB                                    313   C C S [2-CF.sub.3 ]Ph                                                                        NH.sub.2  5-Me     DB                                    314   C C S [2-Me]Th(3)                                                                            NH.sub.2  5-Me     DB                                    315   C C S [4-Me]Th(3)                                                                            NH.sub.2  --       DB                                    316   C C S [2,5-Me.sub.2 ]Fu(3)                                                                   NH.sub.2  --       DB                                    317   C C S [1-Me]Pyr(2)                                                                           NH.sub.2  --       DB                                    318   C C O [2-Me]Ph NH.sub.2  --       DB                                    319   C C O [2-Me]Th(3)                                                                            NH.sub.2  5-Me     DB                                    320   C C O [3-Et, 5-Me]Fu(2)                                                                      NH.sub.2  --       DB                                    321   C C N [2-Me]Ph NH.sub.2  9-Me     DB                                    322   C C N [2-Me]Th(3)                                                                            NH.sub.2  9-Me     DB                                    323   C C S [2-Me]Ph NH.sub.2  --       SB                                    324   S C C [2-Me]Ph NH.sub.2  5,5-Me.sub.2                                                                           SB                                    325   S C C [2-Me]Th(3)                                                                            NH.sub.2  5,6-Me.sub.2                                                                           SB                                    326   S C C [2,5-Me.sub.2 ]Th(3)                                                                   NH.sub.2  --       SB                                    327   S C C [2-Me]Fu(3)                                                                            NH.sub.2  --       SB                                    328   S C C [2-Me]Ph NH(Ac)    --       DB                                    329   S C C [2-Me]Ph NH(Ac)    5-Me     DB                                    330   S C C [2-Me]Th(3)                                                                            NH(Ac)    --       DB                                    331   S C C [2,5-Me.sub.2 ]Fu(3)                                                                   NH(Ac)    --       DB                                    332   N C C [1-Me]Pyr(2)                                                                           NH(Ac)    7-Me     DB                                    333   C C S [2-Me]Ph NH(Ac)    --       DB                                    334   S C C [2-Me]Ph NH(COPen) 5-Me     DB                                    335   S C C [2-Me]Ph N(Ac)(Pr) 5-Me     DB                                    336   S C C [2-Me]Th(3)                                                                            N(Ac)(Pr) --       DB                                    337   C C S [2-Me]Ph N(Ac)(Pr) --       DB                                    338   S C C [2-Me]Ph N(Ac)(CH.sub.2 CH═CH.sub.2)                                                         5-Me     DB                                    339   S C C [2-Me]Th(3)                                                                            N(Ac)(CH.sub.2 CH═CH.sub.2)                                                         5-Me     DB                                    340   S C C [2-Me]Ph NH(Et)    --       DB                                    341   S C C [2-Me]Ph NH(Et)    5-Me     DB                                    342   S C C [2-Me]Th(3)                                                                            NH(Et)    --       DB                                    343   S C C [2,5-Me.sub.2 ]Fu(3)                                                                   NH(Et)    --       DB                                    344   N C C [2,5-Me.sub.2 ]Fu(3)                                                                   NH(Et)    7-Me     DB                                    345   C C S [2-Me]Ph NH(Et)    --       DB                                    346   C C S [1-Me]Pyr(2)                                                                           NH(Et)    --       DB                                    347   S C C [2-Me]Ph NH(Hex)   5-Me     DB                                    348   S C C [2-Me]Ph NH(CH.sub.2 CH═CH.sub.2)                                                            5-Me     DB                                    349   S C C [2-Me]Th(3)                                                                            NH(CH.sub.2 CH═CH.sub.2)                                                            5-Me     DB                                    350   S C C [2-Me]Ph N(Et)(Pr) 5-Me     DB                                    351   S C C [2-Me]Th(3)                                                                            N(Et)(Pr) --       DB                                    352   O C C [2-Cl,3-Me]Th(4)                                                                       N(Et)(Pr) --       DB                                    353   S C C [2-Me]Ph N(Et)(CH.sub.2 CH═CH.sub.2)                                                         5-Me     DB                                    354   S C C [2-Me]Th(3)                                                                            N(Et)(CH.sub.2 CH═CH.sub.2)                                                         5-Me     DB                                    355   S C C [2-Me]Ph NH(CO.sub.2 Et)                                                                         --       DB                                    356   C C S [2-Me]Ph N(Et)(Pr) --       DB                                    357   C C S [3-Et]Th(2)                                                                            N(Et)(Pr) --       DB                                    __________________________________________________________________________

INDUSTRIAL APPLICABILITY

For illustrating superior inhibitory action on gastric acid secretionand superior protective action of gastric mucosa of the compounds of theinvention, pharmacological and acute toxicity tests are shown below,which were conducted using experimental animal models. In Table 3, Table4, Table 5, Table 6, and Table 7, the numbers of test compoundscorrespond to the compound numbers shown in Table 1 and Table 2.

Experiment 1

Inhibitory Action on H⁺ /K⁺ -ATPase Activity

According to the method of Hongo et al. [The Japanese Journal ofPharmacology, 52, p295, (1990)], a microsome fraction prepared fromporcine gastric mucosa was used as a standard enzyme. The standardenzyme (10-20lig protein) and the test compound (0.1-100 μM) dissolvedin dimethylsulfoxide was incubated at 37° C. for 30 minutes in the 50 mMTris-acetate buffer (pH7.4, containing 2 mM magnesium chloride, 5 mMpotassium chloride). The enzyme reaction was started by addingadenosinetriphosphate (ATP). Tris at the final concentration of 2 mM,and the reaction was kept at 37° C. for 15 minutes. The reaction wasstopped by adding chilled 10% trichloroacetic acid. Inorganic phosphatereleased during the reaction was calorimetrically determined accordingto the method of Fiske-Subbarow [The Journal of Biological Chemistry,66, p375, (1925)]. H⁺ /K⁺ -ATPase activity was determined by thedifference of the enzyme activities under the conditions with or withoutpotassium chloride. The inhibitory activities of test compounds weredetermined as the 50% inhibitory concentration (IC₅₀ value) fromreaction-concentration curve, and the results are shown in Table 3.

                  TABLE 3                                                         ______________________________________                                        The inhibitory action on H.sup.+ /K.sup.+ -ATPase activity                    Test Compound                                                                             IC.sub.50 (μM)                                                                      Test Compound IC.sub.50 (μM)                          ______________________________________                                        3               26.0     195           8.8                                    6               12.0     200  hydrochloride                                                                          1.2                                    7               8.0      202  hydrochloride                                                                          9.8                                    9               34.0     206           2.3                                    10              20.0     207  hydrochloride                                                                          9.3                                    12              12.5     211  hydrochloride                                                                          2.4                                    15              3.7      212  hydrochloride                                                                          1.9                                    21              7.4      214           7.0                                    22              1.9      216  hydrochloride                                                                          2.5                                    24              13.5     217  hydrochloride                                                                          4.7                                    26              32.0     219  hydrochloride                                                                          3.6                                    38              4.8      222  hydrochloride                                                                          2.0                                    46              8.4      223  hydrochloride                                                                          4.5                                    54   hydrochloride                                                                            1.0      226           1.9                                    75   hydrochloride                                                                            6.4      230           20.0                                   78              17.0     232           17.0                                   83   hydrochloride                                                                            5.6      234           7.6                                    91              5.6      236           4.7                                    94              3.0      238           2.9                                    96   maleate    17.5     239           26.0                                   104             12.0     245           9.0                                    107             33.0     248           4.7                                    151  hydrochloride                                                                            7.8      254           4.5                                    158  hydrochloride                                                                            13.0     255           6.6                                    163  hydrochloride                                                                            4.6      264           1.2                                    166  hydrochloride                                                                            23.0     271  hydrochloride                                                                          5.2                                    169             5.8      275           24.0                                   176             9.0      291  hydrochloride                                                                          4.8                                    179             4.8      292  hydrochloride                                                                          8.8                                    182             11.0     310           26.0                                   188             10.5     311           8.0                                    189  hydrochloride                                                                            6.8      340  hydrochloride                                                                          33.0                                   191  hydrochloride                                                                            5.2      356  hydrochloride                                                                          8.4                                    192             4.4                                                           ______________________________________                                    

Experiment 2

Inhibition of Gastric Acid Secretion Observed Under Acute Fistula Method

Male Wistar rats (6-8 weeks) fasted for 24 hours (water ad libitum) wereused. The rats were anesthetized by intraperitoneal administration of1.25 g/kg of urethane. The abdomen was incised, and acute gastricfistula was connected to the stomach. Two ml of saline was injected intothe stomach, and recovered every 20 minutes. The gastric acid secretionwas determined by titrating of gastric juice by 150 mM sodium hydroxideup to pH7.0 using an autotitrator. Test compounds (30 mg/kg) suspendedin a 0.5% aqueous sodium carboxymethylcellulose (CMC-Na) solution wereadministered intraduodenally. After 1 hour, gastric acid secretion wasstimulated by subcutaneous administration of histamine dihydrochloridedissolved in saline (10 mg/kg). Inhibition (%) of gastric acid secretionwas determined by calculating cumulative amount of the acid secretionduring two hours after histamine stimulation and then comparing thecumulative amount with that in the control group. In the control group,only 0.5% aqueous CMC-Na solution was administered intraduodenally. Thetest results are shown in Table 4.

                  TABLE 4                                                         ______________________________________                                        Inhibition of gastric acid secretion observed under acute fistula method                  Inhibition             Inhibition                                 Test Compound                                                                             (%)      Test Compound (%)                                        ______________________________________                                        3               82.2     179           52.8                                   6               79.6     182           58.4                                   7               74.9     188           79.1                                   9               90.7     205  hydrochloride                                                                          86.0                                   26              90.8     207  hydrochloride                                                                          67.4                                   46              73.8     214           56.0                                   75   hydrochloride                                                                            73.3     221  hydrochloride                                                                          66.7                                   158  hydrochloride                                                                            83.6     222  hydrochloride                                                                          72.6                                   166  hydrochloride                                                                            54.9     223  hydrochloride                                                                          60.1                                   176             49.9                                                          ______________________________________                                    

Experiment 3

Inhibition of Gastric Acid Secretion Observed Under Stomach PerfusionMethod

Male Sprague Dawrey rats (6-7weeks) fasted for 24 hours were used (waterad libitum). The rats were anesthetized by intraperitonealadministration of 1.25 g/kg of urethane. The abdomen was incised, andgastral cavity was perfused with saline during experiment. The perfusatewas titrated by 10 mM sodium hydroxide up to pH5.5 using an autotitratorin accordance with Stat-method. Gastric acid secretion was stimulated byintravenous administration of histamine dihydrochloride (8 mg/kg/hr).Two hours after histamine stimulation, a test compound 1-10 mg/kg) wasadministered intrapenetorially. The test compound was mixed with smallamount of polysorbate-80, and the mixture was suspended in saline. Thetest compound was evaluated using ID₅₀ (dose showing 50% inhibition ofacid secretion) which was calculated based on inhibition of the acidsecretion observed one hour after administration of the compound. Theresults are shown in Table 5.

                  TABLE 5                                                         ______________________________________                                        Inhibition of gastric acid secretion observed under stomach perfusion         method                                                                                    ID.sub.50              ID.sub.50                                  Test Compound                                                                             (mg/kg)  Test Compound (mg/kg)                                    ______________________________________                                        3               3.4      103           7.4                                    6               5.0      158  hydrochloride                                                                          8.6                                    9               3.1      230           6.2                                    10              4.2      232           3.2                                    12              7.2      234           1.8                                    24              5.4      236           1.4                                    26              2.8      254           1.1                                    43              7.0      255           1.0                                    56              6.5      271  hydrochloride                                                                          2.4                                    78              1.6      291  hydrochloride                                                                          6.4                                    94              5.8      310           3.0                                    96   maleate    8.8      340  hydrochloride                                                                          4.9                                    ______________________________________                                    

Experiment 4

Inhibition of Ethanol-induced Gastric Lesion (Protection of gastricmucosa)

Male Wister rats (6-7weeks, 5 rats per group) fasted for 24 hours wereused (water ad libitum). Test compound (30 mg/kg) suspended in 0.5%aqueous CMC-Na solution was orally administered. In the control group,only 0.5% aqueous CMC-Na solution was administered. Thirty minutes afteradministration, 0.5 ml/100 g body weight of ethanol was orallyadministered to cause gastric lesion. After one hour, the rat was killedby excessive amount of ether, and the stomach was removed and fixed with2% formalin. After fixation, the stomach was dissected along the largecurvature. The size of each of mucosal lesions was measured underdissecting microscope, and the total size of the lesions per rat wasdetermined and used as ulcer index (mm). Inhibition of gastric lesionwas determined by comparing the ulcer index in the control group andtest group. Test results are shown in Table 6.

                  TABLE 6                                                         ______________________________________                                        Inhibition of ethanol-induced gastric lesion                                  Test Compound   Inhibition (%)                                                ______________________________________                                        3                   73.5                                                      158      hydrochloride                                                                            92.4                                                      166      hydrochloride                                                                            49.7                                                      205      hydrochloride                                                                            98.6                                                      216      hydrochloride                                                                            81.7                                                      221      hydrochloride                                                                            73.7                                                      222      hydrochloride                                                                            98.8                                                      236                 91.5                                                      254                 92.4                                                      271      hydrochloride                                                                            99.5                                                      ______________________________________                                    

Experiment 5

Acute Toxicity

Male ICR mice (6 weeks, 3 mice per group) fasted for 16 hours were usedad libitum). A test compound suspended in 5% aqueous gum arabic solutionwas orally administered. After administration, mortality of the animalsobserved during 7 days and approximate lethal dose was determined. Theresults are shown in Table 7.

                  TABLE 7                                                         ______________________________________                                        Acute toxicity                                                                            Ap-                    Ap-                                                    proximate              proximate                                              lethal dose            lethal dose                                Test Compound                                                                             (mg/kg)  Test Compound (mg/kg)                                    ______________________________________                                        3               >2,000   188           >2,000                                 6               >2,000   205  hydrochloride                                                                          >2,000                                 9               >2,000   212  hydrochloride                                                                          >2,000                                 26              >2,000   216  hydrochloride                                                                          >2,000                                 91              >2,000   217  hydrochloride                                                                          >2,000                                 158  hydrochloride                                                                            >2,000   221  hydrochloride                                                                          >2,000                                 166  hydrochloride                                                                            >2,000   222  hydrochloride                                                                          >2,000                                 176             >2,000   236           >2,000                                 179             >2,000   310           >2,000                                 182             >2,000                                                        ______________________________________                                    

The above experiments revealed that the compounds of the presentinvention exert inhibitory actions against H⁺ /K⁺ -ATPase activity andgastric acid secretion and protection of gastric mucosa. Furthermore,the compounds of the invention have low toxicity.

Accordingly, the present invention provides promised anti-ulcer drugshaving inhibitory action on aggressive factors and promoting action ondefensive factors. The anti-ulcer drugs of the invention are thereforeuseful for treating and preventing gastroduodenal ulcers, gastritis,reflex esophagitis, Zollinger-Erison syndrome, and the like.

A pharmaceutical composition containing one or more of the compound(s)(I) of the present invention or pharmaceutically acceptable salts orsolvates thereof as an active ingredient may be used as theabove-mentioned drugs. The pharmaceutical composition can beadministered orally or parenterally in the form of tablets, powders,granules, capsules, pills, syrups, suppositories, injections, externalpreparations, drip injections, and the like. The pharmaceuticalcomposition may be produced by conventional methods without difficulty.For instance, solid preparations for oral use may be prepared by aconventional method using vehicles, binders, disintegrators, lubricants,coloring agents, corrigents, and other commonly used additives. Examplesof such vehicles may include lactose, corn starch, sucrose, glucose,crystalline cellulose, silica, sorbitol, and the like. Examples of suchbinders are polyvinylalcohol, polyvinylether, ethylcellulose, gumarabic, tragacanth, gelatin, hydroxypropylcellulose,hydroxypropylstarch, polyvinylpyrrolidone, and the like. Examples ofdisintegrators may include starch, agar, gelatin, crystalline cellulose,calcium carbonate, sodium bicarbonate, calcium citrate, calciumcarboxymethylcellulose, dextran, and the like. Examples of lubricantsmay include magnesium stearate, talc, polyethyleneglycol, silica,hydrogenated vegetable oil, and the like. The coloring agents may beselected from those which are approved as additives for pharmaceuticalpreparations. Examples of corrigents are powdered cocoa, mentha oil,powdered cinnamon bark, and the like. Tablets and granules may be coatedwith sugar, gelatin, and the like. Injections can readily be prepared bya conventional method, using, if necessary, distilled water,pH-regulating agent, buffering agent, stabilizer, solubilizer, and othercommonly used additives.

Dosage of the compound of the invention, when used as an anti-ulceragent, will vary according to environmental conditions, such as symptom,age, body weight of particular patient and administration route. Thedosage may be usually 3 to 1,500 mg, preferable 5 to 800 mg per day foradults. Increased or decreased dosage is also acceptable, and it may beadministered once a day or after divided into some portions.

The compounds of the invention may conveniently be administered for acontinued period of time, for example, for a week or more.

The phamaceutical composition of the invention containing the compound(I), pharmaceutically acceptable salt or solvate thereof useful for thetreatment of the above-mentioned diseases may also include one or morepharmacologically active constituents, such as antacids (magnesiumcarbonate, magnesium hydroxide, aluminum hydroxide, magnesium aluminateetc.), nonsteroidal anti-inflammatory agents (indomethacin, aspirin,naproxen etc.), steroids, nitrite scavengers (ascorbic acid,aminosulphonic acid etc.), antibiotics (penicillins, tetracyclines etc.)and, if appropriate, enzymes, vitamins, or amino acids.

Special attention should be directed to a combination of the compoundaccording to the invention with other agents inhibiting acid secretion,such as H₂ blockers (cimetidine or ranitidine etc.) or with so-calledperipheral anticholinergic agents (pirenzepine, telenzepine orzolenzepine etc.) with the aim of reinforcing the principal action in anadditive or superadditive sense and/or eliminating or reducing sideeffects, or with antibacterial substances (cephalosporins,tetracyclines, nalidixic acid etc.) with the aim of eradication ofHelicobacter pylori.

BEST MODE FOR CARRYING OUT THE INVENTION

The present invention is illustrated in more detail with workingexamples. However, the present invention is not limited thereto.Starting compounds used in the present invention include novelcompounds. Processes for preparing such starting compounds are alsodescribed below under preparations. In Preparations and Examples, IRmeans infrared spectrum, wherein data is given using cm⁻¹ unit, and themethod used is shown in parentheses, MS means mass spectrum, HRMS meanshigh-resolution mass spectrum wherein the method used is shown inparentheses, and NMR means proton nuclear magnetic resonance spectrum,wherein data is given in ppm and the solvent used is shown inparentheses using following abbreviations.

CDCL Chloroform-d

DMSO Dimethylsulfoxide-d₆

ACET Acetone-d₆

METH Methanol-d₄

Preparation 1

4-(4-Methoxybenzyl)amino-6-methylthieno[3,2-c]pyridine

To a solution of 5.1 g of sodium hydride in oil (prewashed bydecantation with hexane.) in 60 ml of dry tetrahydrofuran was addeddropwise 30 g of triethyl 2-phosphonopropionate over a period of 30minutes under dry argon atmosphere at room temperature. After themixture was stirred for further 1 hour, a solution of 11.8 g of2-thiophenealdehyde in 30 ml of tetrahydrofuran was added dropwise. Themixture was stirred at room temperature for 2 hours. The reactionmixture was poured into water, and extracted with ethyl acetate. Theextract was washed successively with water and saturated saline, driedover anhydrous magnesium sulfate. Drying agent was removed byfiltration, and the solvent was removed under reduced pressure. Theresidue was purified by column chromatography on silica gel to give 11.0g of ethyl 2-methyl-3-(2-thienyl)acrylate as a yellow oil. Next, 150 mlof ethanol and 60 ml of aqueous 2N sodium hydroxide were added to theoil, and the mixture was refluxed for 1 hour. After cooling, ethanol wasremoved under reduced pressure, and the residue was acidified withdilute hydrochloric acid. Crystalline precipitate was collected byfiltration to give 8.2 g of 2-methyl-3-(2-thienyl)acrylic acid as awhite powder.

To a mixture of 8.2 g of 2-methyl-3-(2-thienyl)acrylic acid and 9.5 mlof triethylamine in 45 ml of acetone was added dropwise 7.2 ml of ethylchlorocarbonate over a period of 30 minutes under ice-cooling withstirring. After being stirred for 1 hour, a solution of 5.1 g of sodiumazide in 10 ml of water was added dropwise over 30 minutes, and thenstirred for 1 hour. The reaction mixture was poured into water andextracted with benzene. The extract was washed with water and saturatedsaline, and dried over anhydrous magnesium sulfate. Drying agent wasremoved by filtration, and the solvent was removed under reducedpressure, and then 15 ml of diphenylether was added to the residue. Theresultant solution was added dropwise to a mixture of 14 ml oftri-n-butylamine and 35 ml of diphenylether at 200° C. When addition wascomplete, the reaction mixture was allowed to cool and the crystallineprecipitate was washed with diethyl ether to give 6.2 g of6-methylthieno[3,2-c]pyridin-4(5H)-one as a pale yellow powder.

A solution of 6.2 g of 6-methylthieno[3,2-c]pyridin-4(5H)-one in 30 mlof phosphoryl chloride was heated under reflux for 1 hour. After beingcooled, the excess phosphoryl chloride was removed under reducedpressure, and the residue was poured into ice water, made basic withaqueous 2N sodium hydroxide and extracted with chloroform. The extractwas washed successively with water and saturated saline, and dried overanhydrous magnesium sulfate. The drying agent was removed by filtration,and the solvent was removed under reduced pressure to give 7.0 g of4-chloro-6-methylthieno[3,2-c]pyridine as a brown oily material.

A mixture of 7.0 g of 4-chloro-6-methylthieno[3,2-c]pyridine and 28 mlof 4-methoxybenzylamine was stirred at 170° C. for 4 hours. After beingcooled, the reaction mixture was diluted with 400 ml of chloroform,washed with water and saturated saline, dried over anhydrous magnesiumsulfate. The drying agent was removed by filtration, and the solvent wasremoved under reduced pressure. The residue was purified by columnchromatography on silica gel to give 10 g of the title compound as ayellow oily material.

IR(Neat): 3420, 3080, 3000, 2950, 2920, 2840, 1680, 1590, 1544, 1510,1444, 1400, 1334, 1302, 1248, 1172, 1158, 1108, 1090, 1060, 1030, 888,810, 690; NMR(CDCL): 7.37(2H,d,J=9.0 Hz), 7.18(2H,s), 6.98(1H,s),6.87(2H,d,J=9.0 Hz), 5.10-4.60(1H,br), 4.70(2H,d,J=5.0 Hz), 3.79(3H,s),2.50(3H,s)

Preparation 2

4-Amino-6-methylthieno[3,2-c]pyridine

To a solution of 24 g of4-(4-methoxybenzyl)amino-6-methylthieno[3,2-c]pyridine in 80 ml oftrifluoroacetic acid was added 15 ml of concentrated sulfuric acid, andthe mixture was stirred at ambient temperature for 30 minutes. Thereaction mixture was poured into ice water, rendered alkaline by theaddition of 28% ammonia water and extracted with chloroform. The extractwas washed with water and saturated saline, dried over anhydrousmagnesium sulfate. The drying agent was removed by filtration, and thesolvent was removed under reduced pressure. The residue was purified bycolumn chromatography on silica gel and recrystallized fromchloroform/petroleum ether to give 15 g of the title compound as a whitepowder.

m.p.: 136.0-136.5° C.; IR(KBr): 3470, 3300, 3140, 1632, 1584, 1540,1452, 1420, 1370, 1346, 1270, 1080, 894, 802, 700; NMR(CDCL):7.20(2H,s), 7.00(1H,s), 5.40-5.00(2H,br), 2.45(3H,s)

Preparation 3

7-Aminothieno[2,3-c]pyridine

To a solution of 18 g of thieno[2,3-c]pyridine in 300 ml of chloroformwas added 33 g of 3-chloroperbenzoic acid portionwise with ice-coolingover a period of 1 hour, and the mixture was stirred for further 1 hourunder the same conditions. The reaction mixture was diluted with 400 mlof chloroform, washed successively with water, a saturated sodiumcarbonate solution and saturated saline, and dried over anhydrousmagnesium sulfate. The drying agent was removed by filtration, and thesolvent was removed under reduced pressure to give 16.6 g ofthieno[2,3-c]pyridine-N-oxide as a white powder.

To a solution of 16.6 g of thieno[2,3-c]pyridine-N-oxide in 500 ml ofchloroform was added 25 g of p-toluenesulfonyl chloride portionwise withice-cooling over a period of 1 hour. After the reaction mixture wasstirred for further 30 minutes under the same conditions, 250 ml of 10%ammonia water was added, and stirred at ambient temperature for 16hours. The reaction mixture was diluted with 400 ml of chloroform,washed with water and saturated saline, and dried over anhydrousmagnesium sulfate. The drying agent was removed by filtration, and thesolvent was removed under reduced pressure. The residue was purified bycolumn chromatography on silica gel to give 2.8 g of the title compoundas a brown oily material.

IR(Neat): 3450, 3320, 3150, 1625, 1580, 1552, 1488, 1459, 1400, 1304,1245, 1152, 1110, 1035, 1005, 800, 750; NMR(CDCL): 8.00(1H,d,J=6.0 Hz),7.52(1H,d,J=5.0 Hz), 7.24(1H,d,J=5.0 Hz), 7.11(1H,d,J=6.0 Hz),5.33(2H,brs)

Preparation 4

1-Amino-8-chloro-7-methoxyisoquinoline

To a solution of 1.3 g of 8-chloro-7-methoxyisoquinoline-N-oxide in 40ml of pyridine was added 1.4 g of p-toluenesulfonyl chloride, and themixture was stirred at ambient temperature for 2 hours. The solvent wasremoved under reduced pressure, 20 ml of ethanolamine was added to theresultant residue, and then the mixture was stirred for further 3 hours.The reaction mixture was poured into water, and the crystallineprecipitate was collected by filtration, washed with water, and driedunder reduced pressure to give 0.8 g of the title compound as a yellowpowder.

IR(KBr): 3540, 3300, 3130, 3050, 2950, 2850, 1633, 1600, 1540, 1518,1450, 1423, 1370, 1330, 1290, 1265, 1068, 1025, 957, 818; NMR(CDCL):7.82(1H,d,J=6.0 Hz), 7.60(1H,d,J=9.0 Hz), 7.32(1H,d,J=9.0 Hz),6.90(1H,d,J=6.0 Hz), 6.50-6.02(2H,br), 4.00(3H,s)

Preparation 5

1-Amino-7-methoxyisoquinoline

A solution of 8.0 g of 7-methoxyisoquinoline in 45 ml ofN,N-dimethylaniline was warmed at 60° C., and then 5.9 g of sodium amidewas added. The reaction mixture was heated at 130° C. over a period of 2hours, and stirred for further 1 hour under the same conditions. Afterbeing cooled, the reaction mixture was poured into ice water andextracted with chloroform. The extract was washed with water, and driedover anhydrous magnesium sulfate. The drying agent was removed byfiltration, and the solvent was removed under reduced pressure. Theresidue was purified by column chromatography on silica gel andrecrystallized from benzene to give 5.7 g of the title compound ascolorless flakes.

m.p.: 137.5-138.0° C.; IR(KBr): 3440, 3340, 3150, 3080, 2980, 2850,1652, 1605, 1569, 1516, 1455, 1428, 1385, 1350, 1298, 1241, 1209, 1190,1136, 1085, 1032, 915, 890, 853, 830; NMR(CDCL): 7.84(1H,d,J=6.0 Hz),7.59(1H,d,J=9.0 Hz), 7.20(1H,dd,J=2.0 Hz,9.0 Hz), 7.07(1H,d,J=2.0 Hz),6.95(1H,d,J=6.0 Hz), 5.33(2H,brs), 3.82(3H,s)

Preparation 6

2'-Methyl-2-bromoacetophenone

To a solution of 3 g of 2'-methylacetophenone in 60 ml of acetic acidwas added successively 9.7 ml of 47% hydrobromic acid and 8.6 g ofpyridinium hydrobromide perbromide, and the mixture was stirred at roomtemperature for 1 hour. The reaction mixture was poured into water andextracted with ethyl acetate. The extract was washed with water and asaturated sodium carbonate solution, and dried over anhydrous magnesiumsulfate. The drying agent was removed by filtration, and the solvent wasremoved under reduced pressure to give 5.4 g of the title compound as acolorless oily material.

IR(Neat): 3075, 3030, 2980, 2940, 1682, 1604, 1573, 1490, 1459, 1435,1385, 1358, 1295, 1260, 1210, 1189, 1040, 1008, 978, 754, 735;NMR(CDCL): 7.72-7.05(4H,m), 4.36(2H,s), 2.49(3H,s)

Preparation 7

2-(2-Methylphenyl)imidazo[2,1-a]isoquinoline

A mixture of 3.0 g of 1-aminoisoquinoline, 6.7 g of2'-methyl-2-bromoacetophenone and 17.5 g of sodium bicarbonate in 50 mlof ethanol was refluxed for 2 hours. After being cooled, the reactionmixture was poured into water and extracted with ethyl acetate. Theextract was washed with water and saturated saline, and dried overanhydrous magnesium sulfate. The drying agent was removed by filtration,and the solvent was removed under reduced pressure. The residue waspurified by column chromatography on silica gel and recrystallized fromdichloromethane/petroleum ether to give 4.4 g of the title compound aspale brown prisms.

m.p.: 93.0° C.; IR(KBr): 3070-3020, 2960, 1640, 1604, 1538, 1515, 1480,1458, 1382, 1316, 1208, 1193, 1144, 1120, 1078, 1045, 938, 870, 788,770, 730, 700; NMR(CDCL): 8.90-8.60(1H,m), 8.15-7.83(1H,m),7.79(1H,d,J=7.0 Hz), 7.70-7.10(7H,m), 6.90(1H,d,J=7.0 Hz), 2.54(3H,s)

Preparation 8

9-Methoxy-2-(2-methylphenyl)-5,6-dihydroimidazo[2,1-a]isoquinoline

To a solution of 3.1 g of 7-methoxy-3,4-dihydroisoquinoline in 40 ml ofmethylene chloride was added 7.3 g of 2'-methyl-2-bromoacetophenone, andthe mixture was stirred at room temperature for 4 hours and evaporatedin vacuo. To the resultant residue was added a mixture of 20 ml ofacetic acid and 10.4 g of ammonium acetate, and the mixture was refluxedfor 6 hours. After being cooled, the reaction mixture was poured intoaqueous 2N sodium hydroxide and extracted with ethyl acetate. Theextract was washed with water and saturated saline, and dried overanhydrous magnesium sulfate. The drying agent was removed by filtration,and the solvent was removed under reduced pressure. The residue waspurified by column chromatography on silica gel to give 0.7 g of thetitle compound as a brown viscous material.

IR(Neat): 3070, 3020, 2960, 2910, 2850, 1617, 1578, 1548, 1500, 1482,1465, 1442, 1380, 1332, 1309, 1280, 1252, 1227, 1212, 1180, 1123, 1078,1036, 947, 915, 868, 810, 745; NMR(CDCL): 8.09-7.80(1H,m),7.74(1H,d,J=2.0 Hz), 7.38-7.11(4H,m), 7.05(1H,s), 6.85(1H,dd,J=2.0Hz,6.0 Hz), 4.17(2H,t,J=7.0 Hz), 3.90(3H,s), 3.08(2H,t,J=7.0 Hz),2.53(3H,s)

Preparation 9

9-Methoxy-5-methyl-2-(2-methylphenyl)-5,6-dihydroimidazo[2,1-a]isoquinoline

To a solution of 12 g of 7-methoxy-3-methyl-3,4-dihydroisoquinoline in120 ml of dimethoxyethane was added 16 g of2'-methyl-2-bromoacetophenone, and the mixture was stirred at roomtemperature for 14 hours. The resulting white powder was collected byfiltration to give 13 g of7-methoxy-3-methyl-2-(2-methylphenyl)-3,4-dihydroisoquinolinium bromide.A mixture of this white powder, 80 ml of acetic acid and 12.8 g ofammonium acetate was then refluxed for 3 hours. After being cooled, thereaction mixture was poured into water, rendered alkaline by theaddition of a saturated sodium carbonate solution and extracted withethyl acetate. The extract was washed with water and saturated saline,and dried over anhydrous magnesium sulfate. The drying agent was removedby filtration, and the solvent was removed under reduced pressure. Theresidue was purified by column chromatography on silica gel to give 5.3g of the title compound as a yellow oily material.

IR(Neat): 3060, 3010, 2970, 2940, 2900, 2840, 1612, 1532, 1493, 1482,1462, 1455, 1440, 1372, 1338, 1287, 1274, 1241, 1220, 1170, 1078, 1032,945, 870, 742; NMR(CDCL): 8.02-7.78(1H,m), 7.71(1H,d,J=3.0 Hz),7.40-7.08(5H,m), 6.83(1H,dd,J=3.0 Hz,9.0 Hz), 4.69-4.02(1H,m),3.88(3H,s), 3.38-2.72(2H,m), 2.52(3H,s), 1.52(3H,d,J=7.0 Hz)

Preparation 10

9-Methoxy-5-methyl-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline

To a solution of 4.9 g of9-methoxy-5-methyl-2-(2-methylphenyl)-5,6-dihydroimidazo[2,1-a]isoquinolinein 30 ml of decalin was added 0.97 g of palladium on activated carbon(Pd 10%) and the mixture was refluxed for 6 hours. After being cooledand an addition of 200 ml of chloroform, the mixture was filtered andthe filtrate was evaporated in vacuo. The resultant residue wascrystallized from a mixture of hexane and ethyl acetate(6:1) to give 3.0g of the title compound.

IR(KBr): 2940, 2830, 1618, 1538, 1520, 1498, 1481, 1460, 1440, 1405,1345, 1280, 1259, 1247, 1210, 1174, 1130, 1100, 1030, 872, 830, 800,770, 730; NMR(CDCL): 8.10(1H,d,J=2.0 Hz), 8.07-7.81(1H,m), 7.59(1H,s),7.55(1H,d,J=9.0 Hz), 7.40-7.02(4H,m), 6.79(1H,s), 3.98(3H,s), 2.59(6H,s)

Preparation 11

2-(2-Methyl-3-thienyl)furo[3,2-c]imidazo[1,2-a]pyridine

A solution of 6.1 g of2-(5-bromo-2-methyl-3-thienyl)furo[3,2-c]imidazo[1,2-a]pyridine, whichwas prepared by the reaction of 4-aminofuro[3,2-c]pyridine and5-bromo-3-bromoacetyl-2-methylthiophene in a similar manner to that ofaforementioned Preparation 7, in 50 ml of tetrahydrofuran was addeddropwise to a solution of 3.5 g of lithium aluminum hydride in 50 ml oftetrahydrofuran. When addition was complete, the mixture was refluxedfor 2 hours. After being cooled, excessive lithium aluminum hydride wasdecomposed by the addition of hydrous ether, and the mixture was driedover anhydrous magnesium sulfate. The drying agent was removed byfiltration, and the solvent was removed under reduced pressure to give4.5 g of the title compound as a white powder.

m.p.: 83.5-85.0° C.; IR(KBr): 3370, 3140, 3090, 2910, 1671, 1645, 1574,1510, 1440, 1402, 1338, 1305, 1270, 1240, 1148, 1136, 1079, 1062, 1038,890, 855, 768, 738, 712, 682; NMR(CDCL): 7.98(1H,d,J=8.0 Hz),7.71(1H,d,J=2.0 Hz), 7.65(1H,s), 7.56(1H,d,J=5.0 Hz), 7.31(1H,d,J=2.0Hz), 7.13(1H,d,J=5.0 Hz), 7.08(1H,d,J=8.0 Hz), 2.69(3H,s)

EXAMPLE 1

3-Amino-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline (Compound 3)

In a mixture of 30 ml of acetic acid and 6 ml of water was dissolved 2.5g of 2-(2-methylphenyl)imidazo[2,1-a]isoquinoline with ice-cooling andstirring. A solution of 3.4 g of sodium nitrite in 12 ml of water wasadded portionwise to this solution and then the mixture was stirred atroom temperature for 1 hour. The resulting crude crystals were collectedby filtration and washing. The obtained powder was suspended in amixture of 30 ml of acetic acid and 15 ml of water. To this suspensionwas added portionwise 6.3 g of zinc powder. After 1 hour, the reactionmixture was filtered, the filtrate was rendered alkaline by the additionof 28% ammonia water, and extracted with ethyl acetate. The extract waswashed with water and saturated saline, and dried over anhydrousmagnesium sulfate. The drying agent was removed by filtration, and thesolvent was removed under reduced pressure. The residue was purified bycolumn chromatography on silica gel and recrystallized from ethylacetate/petroleum ether to give 2.1 g of the title compound as orangeneedles.

m.p.: 151.0-153.0° C.; Analysis Calcd. for C₁₈ H₁₅ N₃ ; : C 79.10%, H5.53%, N 15.37%; Found: C 79.29%, H 5.62%, N 15.18%; IR(KBr): 3370,3120-3080, 1645, 1612, 1582, 1528, 1490, 1458, 1382, 1277, 1146, 893,764, 725; NMR(CDCL): 8.76-8.40(1H,m), 7.78(1H,d,J=7.0 Hz),7.69-7.09(7H,m), 6.95(1H,d,J=7.0 Hz), 3.28(2H,brs), 2.37(3H,s);MS(EI)m/z: 273(M⁺), 257, 144;

EXAMPLE 2

3-Amino-2-(2,5-dimethyl-3-furyl)imidazo[1,2-a]thieno[3,2-c]pyridine(Compound 271) hydrochloride

To a solution of 4 g of2-(2,5-dimethyl-3-furyl)imidazo[1,2-a]thieno[3,2-c]pyridine, which wasprepared by the reaction of 4-aminothieno[3,2-c]pyridine and3-bromoacetyl-2,5-dimethylfuran in a similar manner to that ofaforementioned Preparation 7, in 60 ml of dioxane was added dropwise 6ml of isopentyl nitrite at 60° C. When addition was complete, themixture was stirred for further 20 minutes at 70° C. After being cooled,precipitated crystalline was collected by filtration, washed with ether,and added with 9.8 g of zinc powder after addition of 40 ml of aceticacid and 30 ml water under ice-cooling. The mixture was stirred for 16hours. The solution was filtered, the filtrate was rendered alkaline bythe addition of 28% ammonia water, and extracted with ethyl acetate. Theextract was washed with water and saturated saline, and dried overanhydrous magnesium sulfate. The drying agent was removed by filtration,and the solvent was removed under reduced pressure. The residue waspurified by column chromatography on silica gel to give 2.3 g of3-Amino-2-(2,5-dimethyl-3-furyl)imidazo[1,2-a]thieno[3,2-c]pyridine(Compound271) as a pale yellow amorphous solid. To a solution of 2.3 g of theproduct in 100 ml of ether was added a saturated solution of hydrogenchloride in ether, precipitated crystalline was collected by filtration,and recrystallized from ethanol to give 2.0 g of the title compound aspale yellow plates.

m.p.: 210.0-211.5° C.(dec.); IR(KBr): 3370, 3300, 3140, 3050, 2650,1665, 1630, 1623, 1580, 1538, 1445, 1420, 1400, 1378, 1265, 1224, 1000,710; NMR(DMSO): 8.60(1H,d,J=7.5 Hz), 8.48(1H,d,J=5.0 Hz),8.18(1H,d,J=5.0 Hz), 8.08(1H,d,J=7.5 Hz), 6.44(1H,s), 2.42(3H,s),2.35(3H,s)

EXAMPLE 3

Compounds obtained in the same manner as in Examples 1 and 2 arecollectively shown below.

3-Amino-2-(2-fluorophenyl)imidazo[2,1-a]isoquinoline (Compound 1)hydrochloride

m.p.: 221.0-229.0° C.(dec.); IR(KBr): 3500, 3130, 3060, 2950, 2760,2700, 2570, 1670, 1634, 1575, 1550, 1509, 1460, 1430, 1332, 1270, 1214,1109, 790, 760; NMR(DMSO): 9.23-8.89(1H,m), 8.58(1H,d,J=7.8 Hz),8.19-7.18(8H,m)

3-Amino-2-(2-chlorophenyl)imidazo[2,1-a]isoquinoline (Compound 2)

m.p.: 185.0-187.0° C.; IR(KBr): 3360-3150, 1645, 1610, 1580, 1483, 1460,1433, 1380, 1050, 1030, 895, 785, 760; NMR(CDCL): 8.81-8.46(1H,m),8.01-7.15(8H,m), 7.01(1H,d,J=7.0 Hz), 3.60-3.23(2H,brs)

3-Amino-9-fluoro-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline (Compound4)

m.p.: 191.0-192.5° C.; IR(KBr): 3390, 3140, 2930, 1615, 1578, 1559,1523, 1499, 1455, 1419, 1379, 1276, 1248, 1218, 1181, 1140, 1073, 920,868, 813, 755, 723; NMR(CDCL): 8.22(1H,dd,J=2.0 Hz,9.8 Hz), 7.84-7.11(6H,m), 7.77(1H,d,J=7.0 Hz), 6.98(1H,d,J=7.0 Hz), 3.51-3.10(2H,br),2.42(3H,s)

3-Amino-9-chloro-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline (Compound6)

m.p.: 190.0-191.0° C.; IR(KBr): 3380, 3320, 1608, 1582, 1518, 1480,1438, 1408, 1386, 1368, 1104, 826, 726; NMR(DMSO): 8.34(1H,d,J=2.0 Hz),8.16(1H,d,J=7.0 Hz), 7.83(1H,d,J=9.0 Hz), 7.70-7.10(6H,m), 5.10(2H,brs),2.46(3H,s)

3-Amino-10-chloro-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline (Compound7)

m.p.: 147.0-147.5° C.; IR(KBr): 3360, 3100, 1640, 1610, 1575, 1520,1482, 1451, 1377, 1270, 1140, 759; NMR(CDCL): 8.71-8.44(1H,br),7.81-6.70(8H,m), 3.30(2H,s), 2.38(3H,s)

3-Amino-5-methyl-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline (Compound9)

m.p.: 158.0-159.0° C.(dec.); Analysis Calcd. for C₁₉ H₁₇ N₃ : C 79.41%,H 5.96%, N 14.62%; Found: C 79.39%, H 6.07%, N 14.58%; MS(EI)m/z:287(M⁺), 270, 158, 143; HRMS(EI)m/z: 287.14189(Calcd. for: C₁₉ H₁₇ N₃ ;287.3634); IR(KBr): 3410, 3180, 3060, 1647, 1610, 1575, 1533, 1491,1480, 1456, 1390, 1352, 1289, 1260, 1210, 1160, 1040, 945, 868, 828,760, 745, 720; NMR(CDCL): 8.75-8.50(1H,m), 7.58-7.12(7H,m),6.58(1H,brs), 3.32(2H,brs), 2.87(3H,s), 2.35(3H,s)

3-Amino-9-methyl-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline (Compound10)

m.p.: 172.5-173.0° C.; IR(KBr): 3470, 3380, 3300, 3170, 3060, 3030,2960, 2930, 1624, 1582, 1520, 1490, 1450, 1410, 1378, 1302, 1275, 1182,1084, 1034, 945, 910, 855, 822, 770, 726; NMR(CDCL): 8.48(1H,brs),7.75(1H,d,J=7.0 Hz), 7.60-7.12(6H,m), 6.96(1H,d,J=7.0 Hz), 3.30(2H,brs),2.50(3H,s), 2.40(3H,s)

3-Amino-2-(2-methylphenyl)-7-propylimidazo[2,1-a]isoquinoline (Compound13)

m.p.: 137.0-138.0° C.; IR(KBr): 3370, 3120, 2950, 2930, 2860, 1640,1608, 1580, 1520, 1490, 1450, 1382, 1275, 1150, 1080, 763, 720;NMR(CDCL): 8.63(1H,dd,J=2.0 Hz,7.6 Hz), 7.91(1H,d,J=7.8 Hz),7.70-7.20(7H,m), 3.31(2H,brs), 3.00(2H,t,J=8.0 Hz), 2.41(3H,s),2.10-1.46(2H,m), 1.03(3H,t,J=8.0 Hz)

3-Amino-6-isopentyl-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline(Compound 15)

m.p.: 150.5-151.5° C. IR(KBr): 3440, 3110, 3060, 2960, 2930, 2875, 1645,1622, 1608, 1582, 1520, 1492, 1465, 1455, 1392, 1369, 1230, 860,840-810, 760, 724, 690; NMR(CDCL): 8.80-8.60(1H,m), 7.95-7.14(8H,m),3.30(2H,brs), 3.10-2.75(2H,m), 2.40(3H,s), 1.85-1.45(3H,m),1.06(6H,d,J=6.0 Hz)

3-Amino-6-methoxymethyl-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline(Compound 16)

m.p.: 102.5-103.5° C.; IR(KBr): 3430, 3340, 3070, 2940, 2900, 2860,2830, 1650, 1610, 1580, 1522, 1488, 1455, 1445, 1398, 1386, 1352, 1295,1278, 1225, 1200, 1150, 1023, 1096, 1050, 1030, 970, 913, 848, 760, 740,700; NMR(CDCL): 8.85-8.55(1H,m), 8.10-7.29(8H,m), 4.77(2H,s),3.48(3H,s), 3.32(2H,brs), 2.41(3H,s)

3-Amino-2-(2-methylphenyl)-6-(phenoxymethyl)imidazo[2,1-a]isoquinoline(Compound 17)

m.p.: 187.0-188.5° C.; IR(KBr): 3450, 3330, 3170, 3070, 2930, 2880,1651, 1615, 1600, 1590, 1528, 1495, 1480, 1458, 1380, 1350, 1330, 1296,1230, 1175, 1150, 1100, 1080, 1029, 1005, 989, 860, 816, 752, 723, 688;NMR(CDCL): 8.80-8.58(1H,m), 7.91(1H,s), 7.87-6.85(12H,m), 5.25(2H,s),3.30(2H,brs), 2.38(3H,s)

3-Amino-7-hydroxymethyl-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline(Compound 18)

IR(KBr): 3500, 3350, 3230, 3000, 2970, 2900, 1652, 1592, 1525, 1496,1455, 1390, 1320, 1280, 1254, 1220, 1015, 777; NMR(DMSO):8.60-8.01(2H,m), 7.81-7.07(7H,m), 5.58-5.22(1H,m), 5.20-4.66(4H,br),2.48(3H,s)

3-Amino-9-1-hydroxyethyl)-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline(Compound 19)

m.p.: 227.5-229.0° C.; IR(KBr): 3460, 3180, 2980, 2940, 1648, 1624,1590, 1522, 1490, 1445, 1412, 1378, 1272, 1073, 824, 767, 721;NMR(DMSO): 8.46(1H,brs), 8.12(1H,d,J=7.0 Hz), 7.88-7.12(7H,m),5.40(1H,d,J=4.0 Hz), 5.20-4.78(1H,m), 4.98(2H,brs), 2.48(3H,s),1.44(3H,d,J=6.0 Hz)

3-Amino-2-(2-methylphenyl)-9-phenylimidazo[2,1-a]isoquinoline (Compound20) hydrochloride

m.p.: 229.0° C.(dec.); IR(KBr): 3420, 3100, 3060, 2780, 2600, 1668,1630, 1604, 1558, 1491, 1462, 1422, 1300, 1278, 1255, 1160, 900, 830,753, 722, 682; NMR(DMSO): 9.54(1H,s), 8.64(1H,d,J=7.6 Hz),8.20-7.28(12H,m), 2.46(3H,s)

3-Amino-6-(4-methoxyphenyl)-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline(Compound 21)

m.p.: 182.0-183.0° C.; IR(KBr): 3400, 1640, 1610, 1574, 1506, 1454,1394, 1364, 1286, 1246, 1178, 1030, 826, 762; NMR(CDCL):8.92-8.56(1H,m), 7.78(1H,s), 7.70-6.90(11H,m), 3.90(3H,s),3.50-3.06(2H,br), 2.42(3H,s)

3-Amino-6-methoxy-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline (Compound24)

m.p.: 162.0-163.0° C.; IR(KBr): 3430, 3120, 2960, 2850, 1650, 1630,1580, 1521, 1491, 1449, 1383, 1338, 1285, 1259, 1235, 1160, 1120, 1098,1030, 982, 863, 760, 728; NMR(CDCL): 8.72-8.45(1H,m), 8.15-7.85(1H,m),7.71-7.09(7H,m), 3.87(3H,s), 3.78(2H,brs), 2.38(3H,s)

3-Amino-9-methoxy-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline (Compound26)

m.p.: 131.0-132.0° C.; IR(KBr): 3380, 3125, 3000, 2950, 2840, 1616,1577, 1546, 1520, 1503, 1458, 1442, 1380, 1292, 1255, 1233, 1205, 1175,1076, 1033, 870, 803, 752, 720; NMR(CDCL): 8.00(1H,d,J=3.0 Hz),7.68(1H,d,J=7.2 Hz), 7.57(1H,d,J=8.0 Hz), 7.60-7.00(5H,m),6.93(1H,d,J=7.2 Hz), 3.93(3H,s), 3.28(2H,brs), 2.40(3H,s)

3-Amino-9-isopropoxy-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline(Compound 30)

m.p.: 127.0-128.0° C.; IR(KBr): 3400, 3160, 3000, 2940, 1615, 1578,1520, 1500, 1459, 1380, 1335, 1290, 1230, 1112, 955, 825; NMR(CDCL):8.06(1H,d,J=2.0 Hz), 7.72(1H,d,J=7.0 Hz), 7.60(1H,d,J=8.0 Hz),7.50-7.10(5H,m), 6.98(1H,d,J=7.0 Hz), 4.82(1H,qui,J=6.0 Hz),3.29(2H,brs) 2.41(3H,s), 1.40(6H,d,J=6.0 Hz)

3-Amino-8,9-dimethoxy-2-(2-methylphenyl)imnidazo [2,1-a]isoquinoline(Compound 33)

m.p.: 189.0-192.0° C.(dec.); IR(KBr): 3400, 3320, 3070, 3020, 2970,2840, 1620, 1578, 1550, 1520, 1500, 1478, 1443, 1400, 1362, 1279, 1245,1223, 1198, 1160, 1080, 1011, 860, 765, 725; NMR(CDCL): 8.05(1H,s),7.76(1H,d,J=7.0 Hz), 7.57-7.21(4H,m), 7.05(1H,s), 6.93(1H,d,J=7.0 Hz),4.05(3H,s), 3.98(3H,s), 3.25(2H,brs), 2.41(3H,s)

3-Amino-9-ethoxycarbonylmethoxy-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline(Compound 35)

IR(KBr): 3400, 3330, 2980, 1750, 1615, 1575, 1520, 1499, 1440, 1380,1338, 1275, 1195, 1090, 1060, 1015, 910, 855, 820, 750; NMR(CDCL):7.93(1H,d,J=2.4 Hz), 7.67(1H,d,J=7.6 Hz), 7.56(1H,d,J=8.4 Hz),7.48-7.05(5H,m), 6.91(1H,d,J=7.6 Hz), 4.76(2H,s), 4.25(2H,q,J=7.0 Hz),3.32(2H,brs), 2.40(3H,s), 1.29(3H,t,J=7.0 Hz)

3-Amino-9-(2-hydroxyethoxy)-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline(Compound 36)

m.p.: 122.0-124.0° C.; IR(KBr): 3420, 3330, 3050, 2950, 2760, 1620,1583, 1520, 1500, 1458, 1417, 1388, 1340, 1295, 1230, 1080, 1060, 940,900, 818, 770, 725; NMR(DMSO): 8.00(1H,d,J=7.0 Hz), 7.85(1H,d,J=2.0 Hz),7.76(1H,d,J=8.4 Hz), 7.68-7.05(7H,m), 4.99(3H,br), 4.19(2H,t,J=4.6 Hz),4.00-3.70(2H,m), 2.43(3H,s)

3-Amino-9-(2-methoxyethoxy)-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline(Compound 37)

m.p.: 151.0-152.0° C.; IR(KBr): 3410, 3340, 2925, 1645, 1632, 1617,1575, 1550, 1500, 1492, 1452, 1378, 1340, 1298, 1275, 1225, 1200, 1122,1105, 1048, 1023, 935, 858, 820, 764, 720; NMR(CDCL): 7.98(1H,d,J=2.0Hz), 7.65(1H,d,J=7.0 Hz), 7.55(1H,d,J=9.0 Hz), 7.45-7.00(5H,m),6.90(1H,d,J=7.0 Hz), 4.39-4.15(2H,m), 3.85-3.65(2H,m), 3.45(3H,s),3.30(2H,brs), 2.40(3H,s)

3-Amino-6-benzyloxy-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline(Compound 38)

m.p.: 149.0-150.0° C.; IR(KBr): 3470, 3310, 3180, 3090, 2940, 2880,1651, 1622, 1575, 1520, 1495, 1460, 1395, 1375, 1336, 1300, 1285, 1236,1160, 1115, 1092, 1030, 982, 912, 880, 760, 730, 692; NMR(CDCL):8.75-8.50(1H,m), 8.25-8.00(1H,m), 7.70-7.10(12H,m), 5.12(2H,s),3.25(2H,brs), 2.40(3H,s)

9-Acetoxy-3-amino-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline (Compound41)

m.p.: 145.0-146.5° C.; IR(KBr): 3400, 1762, 1612, 1575, 1520, 1495,1373, 1300, 1272, 1209, 1180, 930, 902, 822, 770; NMR(CDCL):8.28(1H,d,J=2.0 Hz), 7.60(1H,d,J=7.0 Hz), 7.52(1H,d,J=8.0 Hz),7.49-7.08(5H,m), 6.80(1H,d,J=7.0 Hz), 4.17(2H,brs), 2.39(3H,s),2.30(3H,s)

3-Amino-9-isobutyryloxy-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline(Compound 43)

m.p.: 138.0-140.0° C.; IR(KBr): 3400, 3300, 2960, 2900, 2860, 1737,1625, 1608, 1550, 1520, 1490, 1470, 1460, 1420, 1385, 1370, 1350, 1300,1273, 1240, 1207, 1180, 1155, 1137, 929, 909, 880, 806, 765, 745;NMR(CDCL): 8.26(1H,d,J=2.0 Hz), 7.64(1H,d,J=7.6 Hz), 8.57(1H,d,J=8.4Hz), 8.57-7.05(5H,m), 6.86(1H,d,J=7.6 Hz), 3.33(2H,brs),3.20-2.45(1H,m), 2.40(3H,s), 1.35(6H,d,J=7.0 Hz)

3-Amino-9-(N,N-dimethylcarbamoyloxy)-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline(Compound 44)

m.p.: 169.0-171.0° C.; IR(KBr): 3420, 3310, 3220, 2990, 2920, 1705,1642, 1626, 1580, 1568, 1518, 1489, 1440, 1410, 1390, 1325, 1300, 1270,1237, 1210, 1170, 1065, 1018, 914, 888, 808, 750; NMR(CDCL):8.18(1H,d,J=2.4 Hz), 7.50(1H,d,J=7.0 Hz), 7.53-7.03(6H,m),6.69(1H,d,J=7.0 Hz), 3.50(2H,brs), 3.08(6H,brs), 2.42(3H,s)

3-Amino-7-benzylthio-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline(Compound 45)

m.p.: 188.0-189.5° C.; IR(KBr): 3380, 3100, 2940, 1640, 1605, 1578,1548, 1522, 1482, 1458, 1438, 1400, 1380, 1293, 1274, 1230, 1200, 1180,1157, 1130, 1068, 1028, 1000, 905, 760, 716, 692; NMR(CDCL):8.53(1H,dd,J=2.0 Hz,6.0 Hz), 7.80(1H,d,J=7.0 Hz), 7.63-7.15(12H,m),4.10(2H,s), 3.30(2H,brs), 2.40(3H,s)

3-Amino-2-(2-methylphenyl)-7-(methylthio)imidazo[2,1-a]isoquinoline(Compound 46)

m.p.: 142.0-144.0° C.; IR(KBr): 3430, 3100, 2950, 1642, 1607, 1483,1458, 1421, 1380, 1344, 1274, 1256, 1203, 1165, 1138, 1048, 962, 898,777; NMR(CDCL): 8.62(1H,dd,J=3.6 Hz,6.0 Hz), 7.93-7.07(8H,m),3.55-3.15(2H,br), 2.93(3H,s), 2.40(3H,s)

6-Acetyl-3-amino-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline (Compound47)

m.p.: 190.0-191.0° C.; IR(KBr): 3410, 3230, 2960, 1672, 1616, 1595,1490, 1454, 1408, 1368, 1336, 1324, 1289, 1185, 1160, 767; NMR(DMSO):9.10-8.75(1H,m), 9.04(1H,s), 8.63-8.31(1H,m), 7.90-7.09(6H,m),5.42(2H,brs), 2.79(3H,s), 2.47(3H,s)

3-Amino-7-(p-anisoyl)-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline(Compound 48)

m.p.: 164.0-165.0° C.; IR(KBr): 3400, 3330, 1650, 1600, 1572, 1514,1422, 1373, 1312, 1278, 1260, 1175, 1142, 1015, 965, 887, 846, 794, 754;NMR(CDCL): 8.93-8.61(1H,m), 8.02-6.75(12H,m), 3.85(3H,s), 3.46(2H,brs),2.40(3H,s)

3-Amino-2-(2-methylphenyl)imidazo[2,1-a]isoquinolin-7-carboxylic acid(Compound 49) hydrochloride

m.p.: 231.0-233.5° C.; IR(KBr): 3450-3340, 2950-2800, 2720, 2680, 2630,1710, 1670, 1627, 1548, 1496, 1458, 1396, 1270, 1220, 1128, 792;NMR(DMSO): 9.55-9.25(1H,m), 8.95-8.32(3H,m), 7.98(1H,t,J=8.0 Hz),7.50(4H,s), 2.44(3H,s)

3-Amino-6-methoxycarbonyl-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline(Compound 50)

m.p.: 185.0-186.0° C.; IR(KBr): 3410, 3330, 3180, 2960, 1712, 1633,1607, 1586, 1485, 1455, 1439, 1401, 1330, 1302, 1282, 1244, 1198, 1156,1045, 1030, 928, 760; NMR(CDCL): 8.95-8.52(2H,m), 8.64(1H,s),7.73-7.05(6H,m), 3.93(3H,s), 3.40(2H,brs), 2.37(3H,s)

3-Amino-7-cyano-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline (Compound52)

m.p.: 190.0-191.0° C.; IR(KBr): 3400, 3140, 2250, 1642, 1600, 1576,1528, 1492, 1450, 1378, 1325, 1275, 1218, 1150, 928, 768; NMR(CDCL):8.78(1H,dd,J=2.0 Hz,7.0 Hz), 7.99(1H,d,J=7.0 Hz), 7.90-7.01(7H,m),3.57(2H,brs), 2.44(3H,s)

3-Amino-7-diethylamino-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline(Compound 54)

IR(KBr): 3430, 3320, 3060, 2980, 2940, 2870, 2830, 1640, 1600, 1556,1486, 1450, 1380, 1250, 1210, 1135, 1030, 945, 780-750; NMR(CDCL):8.40(1H,brd,J=7.0 Hz), 7.92-7.10(8H,m), 3.52-2.93(2H,br),3.19(4H,q,J=7.0 Hz), 2.43(3H,s), 1.05(6H,t,J=7.0 Hz); (hydrochloridem.p.:211.0-215.0° C.)

3-Amino-10-chloro-9-methoxy-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline(Compound 55)

m.p.: 180.5-181.5° C.; IR(KBr): 3180, 3010, 2940, 2840, 1648, 1603,1573, 1538, 1490, 1460, 1440, 1409, 1370, 1280, 1254, 1222, 1180, 1154,1118, 1067, 1040, 1010, 952, 855, 800, 753, 720; NMR(CDCL):7.55(1H,d,J=7.0 Hz), 7.45(1H,d,J=8.0 Hz), 7.40-7.12(4H,m),7.04(1H,d,J=8.0 Hz), 6.78(1H,d,J=7.0 Hz), 3.95(3H,s), 3.40(2H,brs),2.50(3H,s)

3-Amino-9-methoxy-5-methyl-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline(Compound 56)

m.p.: 165.0-166.0° C.; IR(KBr): 3400, 3280, 3160, 1675, 1613, 1524,1495, 1455, 1436, 1390, 1355, 1296, 1240, 1180, 1150, 1098, 1032, 890,850, 765, 728; NMR(CDCL): 8.01(1H,d,J=2.6 Hz), 7.62-7.25(5H,m),7.09(1H,dd,J=2.6 Hz,9.0 Hz), 6.61(1H,s), 3.94(3H,s), 3.32(2H,brs),2.94(3H,s), 2.40(3H,s)

3-Amino-2-(3-methylphenyl)imidazo[2,1-a]isoquinoline (Compound 57)hydrochloride

m.p.: 192.0° C.(dec.); IR(KBr): 3320, 3170, 3060, 2940, 2720, 1662,1615, 1549, 1496, 1460, 1425, 1335, 794, 685; NMR(DMSO):9.42-9.08(1H,m), 8.58(1H,d,J=7.0 Hz), 8.20-7.00(8H,m), 2.38(3H,s)

3-Amino-2-(2-ethylphenyl)imidazo[2,1-a]isoquinoline (Compound 59)hydrochloride

m.p.: 215.0-216.0° C.; IR(KBr): 3450, 3120, 2980, 2940, 2890, 2600,1668, 1630, 1550, 1498, 1460, 1426, 1330, 1281, 1250, 1168, 868, 794,770, 680; NMR(DMSO): 9.15-8.88(1H,m), 8.65(1H,d,J=7.0 Hz),8.29-7.70(4H,m), 7.50(4H,s), 2.78(2H,q,J=7.0 Hz), 1.11 (3H,t,J=7.0 Hz)

3-Amino-2-(2-trifluoromethylphenyl)imidazo[2,1-a]isoquinoline (Compound60) hydrochloride

m.p.: 189.0-194.0° C.(dec.); IR(KBr): 3470, 3270, 3150, 3050, 2920,2800, 2730, 2680, 1668, 1632, 1608, 1582, 1550, 1500, 1460, 1439, 1425,1318, 1270, 1241, 1171, 1120, 1059, 1033, 970, 798, 778, 675; NMR(DMSO):8.92-8.70(1H,m), 8.55(1H,d,J=7.4 Hz), 8.30-7.60(8H,m)

3-Amino-2-(2,4-dimethylphenyl)imidazo[2,1-a]isoquinoline (Compound 62)m.p.: 191.0-192.5° C.; IR(KBr): 3100, 2920, 1645, 1615, 1583, 1529,1505, 1490, 1458, 1380, 1275, 1145, 825, 770; NMR(CDCL):8.72-8.50(1H,m), 7.90-6.89(8H,m), 3.28(2H,brs), 2.34(6H,s)

3-Amino-2-(4-chloro-2-methylphenyl)imidazo[2,1-a]isoquinoline (Compound66)

m.p.: 223.0-224.0° C.; IR(KBr): 3390, 3250, 3120, 3070, 3040, 2930,1645, 1615, 1580, 1525, 1487, 1459, 1437, 1415, 1380, 1315, 1284, 1204,1173, 1145, 1100, 1029, 985, 893, 866, 824, 770, 680; NMR(DMSO):8.43-8.19(1H,m), 8.03(1H,d,J=7.0 Hz), 7.87-7.23(6H,m), 7.10(1H,d,J=7.0Hz), 5.04(2H,brs), 2.41(3H,s)

3-Amino-2-(4-hydroxy-2-methylphenyl)imidazo[2,1-a]isoquinoline (Compound68)

m.p.: 273.0-276.0° C.(dec.); IR(KBr): 3400, 3330, 3050, 3000, 2910,2770, 2670, 2600, 1638, 1608, 1510, 1500, 1453, 1380, 1300, 1245, 1165,948, 899, 860, 810, 785, 740; NMR(DMSO): 9.35(1H,s), 8.50-8.28(1H,m),8.09(1H,d,J=7.0 Hz), 7.92-7.02(5H,m), 6.82-6.58(2H,m), 4.82(2H,brs),2.33(3H,s)

3-Amino-2-(4-methoxy-2-methylphenyl)imidazo[2,1-a]isoquinoline (Compound69) hydrochloride

m.p.: 215.5-217.5° C.; IR(KBr): 3380, 3090, 2920, 2830, 2750, 2680,2600, 1665, 1610, 1567, 1545, 1510, 1460, 1420, 1292, 1245, 1162, 1068,1038, 790; NMR(DMSO): 9.28-8.94(1H,m), 8.65(1H,d,J=7.0 Hz),8.29-7.70(4H,m), 7.48(1H,d,J=9.0 Hz), 7.09-6.80(2H,m), 5.60-4.55(2H,br),3.85(3H,s), 2.83(3H,s)

2-(4-Acetoxy-2-methylphenyl)-3-aminoimidazo[2,1-a]isoquinoline (Compound70) hydrochloride

m.p.: 201.0-205.0° C.; IR(KBr): 3600, 3450, 3350, 3150, 2910, 2640,1750, 1662, 1625, 1547, 1500, 1453, 1420, 1370, 1203, 1158, 1013, 950,904, 788; NMR(DMSO): 9.13-8.90(1H,m), 8.61(1H,d,J=7.0 Hz),8.28-7.50(5H,m), 7.31-7.08(2H,m), 2.40(3H,s), 2.31(3H,s)

3-Amino-2-(2,4,6-trimethylphenyl)imidazo[2,1-a]isoquinoline (Compound71)

m.p.: 103.0-105.0° C.; IR(KBr): 3420, 3320, 3150, 3070, 3020, 2970,2930, 2860, 1645, 1615, 1585, 1520, 1485, 1450, 1375, 1311, 1275, 1210,1139, 1085, 1025, 983, 891, 850, 784, 745, 685; NMR(CDCL):8.75-8.52(1H,m), 7.83(1H,d,J=7.0 Hz), 7.74-7.32(3H,m), 7.02(1H,d,J=7.0Hz), 6.95(2H,s), 3.33-2.95(2H,br), 2.31(3H,s), 2.12(6H,s)

3-Amino-2-(3-methyl-2-thienyl)imidazo[2,1-a]isoquinoline (Compound 73)

m.p.: 174.0-175.0° C.; IR(KBr): 3400, 3340, 3100, 3060, 2920, 1640,1605, 1519, 1482, 1458, 1371, 935, 890, 833, 785, 732, 712, 673;NMR(CDCL): 8.78-8.52(1H,m), 7.84-7.41(4H,m), 7.29(1H,d,J=5.0 Hz),6.99(1H,d,J=7.4 Hz), 6.98(1H,d,J=5.0 Hz), 3.41(2H,brs), 2.44(3H,s)

3-Amino-6-methoxy-2-(3-methyl-2-thienyl)imidazo[2,1-a]isoquinoline(Compound 74)

m.p.: 143.0-146.0° C.; IR(KBr): 3440, 3110, 2950, 1652, 1627, 1590,1521, 1470, 1450, 1381, 1330, 1298, 1257, 1235, 1161, 1125, 1099, 1028,995, 960, 924, 861, 762; NMR(CDCL): 8.70-8.46(1H,m), 8.13-7.91(1H,m),7.78-7.42(2H,m), 7.27(1H,s), 7.22(1H,d,J=5.0 Hz), 6.93(1H,d,J=5.0 Hz),3.92(3H,s), 3.62-3.08(2H,br), 2.45(3H,s)

3-Amino-9-methoxy-2-(3-methyl-2-thienyl)imidazo[2,1-a]isoquinoline(Compound 75)

IR(KBr): 3420, 2930, 1616, 1518, 1500, 1439, 1370, 1337, 1297, 1275,1229, 1180, 1139, 1026, 905, 854, 820; NMR(CDCL): 7.99(1H,d,J=2.4 Hz),7.64(1H,d,J=7.6 Hz), 7.53(1H,d,J=8.2 Hz), 7.35-7.10(2H,m),6.96(1H,d,J=8.2 Hz), 6.94(1H,d,J=6.4 Hz), 3.96(3H,s), 3.55-3.30(2H,br),2.42(3H,s); (hydrochloride m.p.: 195.0° C.(dec.))

3-Amino-2-(4-methyl-2-thienyl)imidazo[2,1-a]isoquinoline (Compound 76)

m.p.: 152.0-155.0° C.; IR(KBr): 3460, 3310, 3175, 3070, 2930, 1645,1623, 1584, 1552, 1520, 1488, 1459, 1375, 1265, 1212, 1182, 1155, 922,890, 848, 788, 720; NMR(CDCL): 8.75-8.45(1H,m), 7.69(1H,d,J=7.0 Hz),7.69-7.47(3H,m), 7.33(1H,d,J=1.0 Hz), 6.89(1H,d,J=7.0 Hz),6.84(1H,d,J=1.0 Hz), 3.53-3.08(2H,b 2.30(3H,s)3-Amino-2-(3-ethyl-2-thienyl)imidazo[2,1-a]isoquinoline (Compound 77)IR(KBr): 3410, 3300, 2970, 2930, 2870, 1642, 1610, 1588, 1519, 1483,1457, 1370, 1324, 1272, 1210, 1175, 1138, 888, 780; NMR(CDCL):8.68-8.39(1H,m), 7.66(1H,d,J=7.0 Hz), 7.58-7.30(3H,m), 7.22(1H,d,J=5.0Hz), 6.98(1H,d,J=5.0 Hz), 6.86(1H,d,J=7.0 Hz), 3.38(2H,brs),2.83(2H,q,J=7.0 Hz), 1.22(3H,t,J=7.0 Hz)

3-Amino-2-(2-methyl-3-thienyl)imidazo[2,1-a]isoquinoline (Compound 78)

m.p.: 124.0-124.5° C.; IR(KBr): 3400, 3330, 3090, 2910, 1638, 1606,1518, 1482, 1455, 1440, 1373, 1230, 1209, 1170, 1139, 1084, 890, 858,784, 732, 690; NMR(CDCL): 8.75-8.45(1H,m), 7.78(1H,d,J=7.0 Hz),7.70-7.40(3H,m), 7.23(1H,d,J=5.0 Hz), 7.10(1H,d,J=5.0 Hz),6.98(1H,d,J=7.0 Hz), 3.30(2H,brs), 2.62(3H,s)

3-Amino-2-(4-methyl-3-thienyl)imidazo[2,1-a]isoquinoline (Compound 81)

m.p.: 155.5-156.0° C.; IR(KBr): 3440, 3300, 3150, 3050, 1640, 1620,1580, 1548, 1518, 1485, 1455, 1370, 1360, 1262, 1210, 1180, 1154, 890,848, 790, 720; NMR(CDCL): 8.72-8.48(1H,m), 7.67-7.44(4H,m),7.28(1H,brs), 6.86-6.73(2H,m), 3.30(2H,brs), 2.27(3H,s)

3-Amino-2-(2,5-dimethyl-3-thienyl)imidazo[2,1-a]isoquinoline (Compound83) hydrochloride

m.p.: 233.0° C.(dec.); IR(KBr): 3350, 3140, 3050, 2910, 2850, 2750,2660, 1665, 1625, 1545, 1440, 1420, 1380, 1328, 1305, 1246, 1110, 790;NMR(DMSO): 9.20-8.97(1H,m), 8.62(1H,d,J=7.0 Hz), 8.26-7.68(4H,m),7.01(1H,s), 2.48(6H,s)

3-Amino-2-(2-chloro-3-methyl-4-thienyl)imidazo[2,1-a]isoquinoline(Compound 85)

m.p.: 167.0-170.0° C.(dec.); IR(KBr): 3400, 3150, 3100, 1640, 1613,1595, 1520, 1477, 1455, 1369, 1352, 1138, 1005, 763, 680; NMR(CDCL):8.71-8.42(1H,m), 7.71(1H,d,J=7.0 Hz), 7.70-7.38(3H,m), 7.13(1H,s),6.99(1H,d,J=7.0 Hz), 3.42(2H,br), 2.35(3H,s)

3-Amino-7-bromo-2-(2-chloro-3-methyl-4-thienyl)imidazo[2,1-a]isoquinoline(Compound 86)

IR(KBr): 3420, 3100, 2930, 1638, 1615, 1596, 1513, 1478, 1435, 1400,1370, 1342, 1257, 1211, 1102, 1030, 961, 895, 858, 776, 740; NMR(CDCL):8.55(1H,brd,J=7.4 Hz), 7.93-7.62(2H,m), 7.55-7.19(2H,m), 7.15(1H,s),3.62-3.23(2H,br), 2.29(3H,s)

3-Amino-2-(3-methyl-2-furyl)imidazo[2,1-a]isoquinoline (Compound 88)

m.p.: 183.0-185.0° C.(dec.); IR(KBr): 3420, 3325, 2925, 1640, 1600,1545, 1521, 1481, 1458, 1367, 1168, 1078, 885, 795, 746, 725; NMR(DMSO):8.53-8.30(1H,m), 8.10(1H,d,J=7.0 Hz), 7.95-7.48(4H,m), 7.18(1H,d,J=7.0Hz), 6.47(1H,d,J=2.0 Hz), 5.42(2H,brs), 2.46(3H,s)

3-Amino-2-(2,5-dimethyl-3-furyl)imidazo[2,1-a]isoquinoline (Compound 91)

m.p.: 135.0-136.0° C.(dec.); IR(KBr): 3410, 3310, 2920, 1640, 1594,1520, 1482, 1452, 1374, 1268, 1212, 1186, 1080, 994, 922, 890, 784, 740;NMR(CDCL): 8.80-8.54(1H,m), 7.77(1H,d,J=7.0 Hz), 7.70-7.40(3H,m),6.95(1H,d,J=7.0 Hz), 6.28(1H,s), 3.22(2H,brs), 2.54(3H,s), 2.29(3H,s)

3-Amino-2-(1-methyl-2-pyrrolyl)imidazo[2,1-a]isoquinoline (Compound 94)

m.p.: 134.0-136.0° C.(dec.); IR(KBr): 3400, 3320, 3090, 1638, 1607,1585, 1532, 1515, 1492, 1453, 1374, 1313, 1289, 1262, 1177, 1086, 1053,970, 892, 780, 718, 700; NMR(CDCL): 8.70-8.35(1H,m), 7.61(1H,d,J=7.0Hz), 7.58-7.33(3H,m), 6.88(1H,d,J=7.0 Hz), 6.70(1H,t,J=2.0 Hz),6.34-6.12(2H,m), 3.87(3H,s), 3.44(2H,brs)

3-Amino-2-(2-methylphenyl)-5,6-dihydroimidazo[2,1-a]isoquinoline(Compound 96) maleate

m.p.: 157.0-158.0° C.; IR(KBr): 3350, 3210, 3060, 2960, 2920, 2840,2800, 2740, 1655, 1585, 1480, 1360, 1210, 1192, 1010-988, 868, 760, 700;NMR(DMSO): 8.10-7.72(1H,m), 7.67-7.27(7H,m), 6.05(2H,s), 4.23(2H,t,J=7.0Hz), 3.28(2H,t,J=7.0 Hz), 2.35(3H,s)

3-Amino-9-fluoro-2-(2-methylphenyl)-5,6-dihydroimidazo[2,1-a]isoquinoline(Compound 97)

m.p.: 157.5-158.0° C.; IR(KBr): 3410, 3150, 2920, 1620, 1575, 1538,1496, 1456, 1356, 1315, 1270, 1258, 1202, 1174, 1070, 911, 876, 862,799, 766, 722; NMR(CDCL): 7.75(1H,dd,J=2.0 Hz,10 Hz), 7.50-6.70(6H,m),3.98(2H,t,J=7.0 Hz), 3.50-2.90(2H,br), 3.09(2H,t,J=7.0 Hz), 2.40(3H,s)

3-Amino-8-chloro-2-(2-methylphenyl)-5,6-dihydroimidazo[2,1-a]isoquinoline(Compound 98) hydrochloride

m.p.: 199.0-201.0° C.(dec.); IR(KBr): 3425, 3320, 3130, 2930, 2850,2760, 2700, 2660, 2620, 1640, 1560, 1504, 1480, 1453, 1314, 1290, 1193,1110, 1084, 850, 823, 764; NMR(DMSO): 8.42(1H,d,J=8.0 Hz),7.82-7.27(6H,m), 4.31 (2H,t,J=7.0 Hz), 3.31 (2H,t,J=7.0 Hz), 2.39(3H,s)

3-Amino-9-bromo-2-(2-methylphenyl)-5,6-dihydroimidazo[2,1-a]isoquinoline(Compound 99)

m.p.: 167.0-170.0° C.; IR(KBr): 3450, 3370, 2960, 2930, 1610, 1588,1530, 1490, 1460, 1431, 1387, 1347, 1317, 1250, 1224, 1203, 1150, 1100,1068, 1040, 885, 812, 792, 765, 725; NMR(CDCL): 8.18(1H,d,J=2.0 Hz),7.50-6.90(6H,m), 3.98(2H,t,J=7.0 Hz), 3.48-2.88(2H,br), 3.07(2H,t,J=7.0Hz), 2.40(3H,s)

3-Amino-5-methyl-2-(2-methylphenyl)-5,6-dihydroimidazo[2,1-a]isoquinoline(Compound 100)

IR(KBr): 3400, 3300, 3120, 3050, 2960, 2920, 1605, 1572, 1530, 1485,1475, 1450, 1412, 1377, 1353, 1265, 1250, 1200, 1150, 1083, 1030, 978,940, 755, 720; NMR(CDCL): 8.17-7.88(1H,m), 7.50-7.05(7H,m),4.80-4.20(1H,m), 3.42(1H,dd,J=6.0 Hz,16.0 Hz), 3.20(2H,br),2.78(1H,dd,J=1.6 Hz,16.0 Hz), 2.39(3H,s), 1.24(3H,d,J=7.0 Hz)

3-Amino-9-methyl-2-(2-methylphenyl)-5,6-dihydroimidazo[2,1-a]isoquinoline(Compound 102)

m.p.: 141.5-143.0° C.; IR(KBr): 3420, 3300, 3150, 3050, 2900, 1632,1615, 1602, 1570, 1532, 1490, 1450, 1378, 1350, 1338, 1315, 1270, 1218,1186, 1095, 1036, 943, 916, 865, 810, 762, 720; NMR(CDCL): 7.87(1H,brs),7.50-6.95(6H,m), 3.93(2H,t,J=7.0 Hz), 3.17(2H,brs), 3.04(2H,t,J=7.0 Hz),2.39(3H,s), 2.32(3H,s)

3-Amino-5,5-dimethyl-2-(2-methylphenyl)-5,6-dihydroimidazo[2,1-a]isoquinoline(Compound 104)

m.p.: 151.0-152.0° C.(dec.); IR(KBr): 3440, 3280, 3060, 2960, 2925,2760, 1680, 1602, 1570, 1488, 1470, 1460, 1435, 1370, 1341, 1300, 1282,1262, 1239, 1189, 1162, 1120, 1100, 983, 955, 815, 760, 723; NMR(CDCL):8.20-8.00(1H,m), 8.10-7.80(2H,br), 7.55-7.00(7H,m), 2.93(1H,d,J=16.0Hz), 2.59(1H,d,J=16.0 Hz), 2.35(3H,s), 1.70(3H,s), 1.65(3H,s)

3-Amino-6,7-dimethyl-2-(2-methylphenyl)-5,6-dihydroimidazo[2,1-a]isoquinoline(Compound 105)

m.p.: 107.0-110.0° C.(dec.); IR(KBr): 3420, 3300, 3050, 2970, 2940,2880, 1675, 1617, 1602, 1580, 1490, 1458, 1418, 1380, 1325, 1150, 753;NMR(CDCL): 8.07-7.72(1H,m), 7.57-6.91(6H,m), 4.05-2.90(5H,m),2.41(3H,s), 2.35(3H,s), 1.20(3H,d,J=7.0 Hz)

3-Amino-2-(4-hydroxy-2-methylphenyl)-5,6-dihydroimidazo[2,1-a]isoquinoline(Compound 107)

m.p.: 262.0-265.0° C.(dec.); IR(KBr): 3410, 3330, 3050, 2960, 2760,2650, 2580, 1605, 1500, 1456, 1419, 1380, 1350, 1300, 1245, 1200, 1188,1168, 910, 864, 764; NMR(DMSO): 9.22(1H,s), 7.88-7.62(1H,m),7.40-7.03(4H,m), 6.80-6.50(2H,m), 4.50(2H,brs), 4.00(2H,t,J=7.0 Hz),3.09(2H,t,J=7.0 Hz), 2.30(3H,s)

3-Amino-2-(5-bromo-4-hydroxy-2-methylphenyl)-5,6-dihydroimidazo[2,1-a]isoquinoline(Compound 108)

m.p.: 285.0° C.(dec.); IR(KBr): 3360, 3140, 2920, 1654, 1610, 1560,1503, 1480, 1455, 1421, 1357, 1298, 1248, 1220, 864, 815, 772;NMR(DMSO): 9.73(1H,s), 8.11-7.82(1H,m), 7.65-7.10(3H,m),6.98-6.64(2H,m), 5.88-5.40(2H,br), 4.28(2H,t,J=7.0 Hz), 3.29(2H,t,J=7.0Hz), 2.22(3H,s)

3-Amino-5-methyl-2-phenylimidazo[1,2-a]thieno[3,2-c]pyridine (Compound230)

m.p.: 193.0-194.0° C.; IR(KBr): 3370, 3280, 3090, 1620, 1596, 1580,1560, 1530, 1485, 1442, 1380, 1360, 1285, 1230, 1195, 990, 915, 878,818, 792, 770, 730, 710, 685; NMR(DMSO): 8.35-8.00(2H,m),7.86-7.63(2H,m), 7.62-7.20(3H,m), 7.06(1H,s), 4.58(2H,brs), 3.02(3H,s)

3-Amino-2-(2-hydroxyphenyl)-5-methylimidazo[1,2-a]thieno[3,2-c]pyridine(Compound 231)

m.p.: 199.5-201.0° C.; IR(KBr): 3400, 3320, 1630, 1570, 1538, 1490,1455, 1410, 1373, 1290, 1250, 1013, 818, 754, 710; NMR(DMSO):8.38-8.20(1H,m), 7.78(2H,s), 7.37-6.72(4H,m), 4.83(2H,brs),3.60-2.92(1H,br), 3.05(3H,s)

3-Amino-2-(2-chlorophenyl)imidazo[1,2-a]thieno[3,2-c]pyridine (Compound232)

m.p.: 180.0-181.0° C.; IR(KBr): 3330, 3170, 3080, 1626, 1578, 1482,1432, 1409, 1402, 1352, 1294, 1252, 1268, 1188, 1168, 1150, 1046, 1030,954, 900, 756, 702; NMR(CDCL): 7.97(1H,d,J=5.0 Hz), 7.96(1H,d,J=7.0 Hz),7.87-7.60(1H,m), 7.53(1H,d,J=5.0 Hz), 7.50-7.21(3H,m), 7.21(1H,d,J=7.0Hz), 3.42(2H,brs)

3-Amino-2-(2-methylphenyl)imidazo[1,2-a]thieno[3,2-c]pyridine (Compound234)

m.p.: 136.0-137.0° C.; Analysis Calcd. for C₁₆ H₁₃ N₃ S; C 68.79%, H4.69%, N 15.04%; Found: C 68.53%, H 4.82%, N 14.75%; MS(EI)m/z: 279(M⁺),263, 150, 135, 83; HRMS(EI)m/z: 279.08338(Calcd. for: C₁₆ H₁₃ N₃ S;279.3588); IR(KBr): 3350-3200, 3090, 2910, 1628, 1580, 1513, 1490, 1478,1450, 1410, 1400, 1351, 1294, 1265, 1185, 1168, 1080, 1010, 953, 765,743, 700; NMR(CDCL): 7.95(1H,d,J=5.8 Hz), 7.85(1H,d,J=7.0 Hz),7.49(1H,d,J=5.8 Hz), 7.50-7.10(5H,m), 3.30(2H,brs), 2.39(3H,s)

3-Amino-8-bromo-2-(2-methylphenyl)imidazo[1,2-a]thieno[3,2-c]pyridine(Compound 235)

m.p.: 221.5-222.0° C.; IR(KBr): 3360, 3080, 1627, 1605, 1580, 1480,1450, 1400, 1350, 1290, 1270, 1200, 1170, 1152, 980, 923, 826, 763, 726;NMR(CDCL): 7.95(1H,s), 7.91(1H,d,J=7.5 Hz), 7.50-7.23(4H,m),7.10(1H,d,J=7.5 Hz), 3.28(2H,brs), 2.40(3H,s)

3-Amino-5-methyl-2-(2-methylphenyl)imidazo[1,2-a]thieno[3,2-c]pyridine(Compound 236)

m.p.: 185.0-185.5° C.; Analysis Calcd. for C₁₇ H₁₅ N₃ S; : C 69.60%, H5.15%, N 14.32%; Found: C 69.34%, H 5.20%, N 14.11%; MS(EI)m/z: 293(M⁺),277, 164, 149, 83; HRMS(EI)m/z: 293.09827(Calcd. for: C₁₇ H₁₅ N₃ S;293.3856); IR(KBr): 3390, 3280, 3170, 3070, 1632, 1574, 1530, 1488,1440, 1376, 1286, 1250, 1170, 1012, 882, 810, 760, 718, 700; NMR(CDCL):7.70(1H,d,J=5.0 Hz), 7.40-7.00(5H,m), 6.62(1H,s), 3.22(2H,brs),2.87(3H,s), 2.28(3H,s)

3-Amino-5-ethyl-2-(2-methylphenyl)imidazo[1,2-a]thieno[3,2-c]pyridine(Compound 238)

m.p.: 178.0-179.0° C.; IR(KBr): 3390, 3330, 3090, 2960, 2940, 2910,2870, 1630, 1580, 1564, 1534, 1485, 1460, 1434, 1402, 1375, 1289, 1275,1245, 1176, 1153, 1076, 1000, 870, 830, 772, 705; NMR(CDCL):7.80(1H,d,J=5.0 Hz), 7.44-7.03(5H,m), 6.80(1H,s), 3.40(2H,q,J=7.0 Hz),3.38-3.13(2H,br), 2.32(3H,s), 1.37(3H,t,J=7.0 Hz)

3-Amino-5,6-dimethyl-2-(2-methylphenyl)imidazo[1,2-a]thieno[3,2-c]pyridine(Compound 239)

m.p.: 173.5-175.0° C.; IR(KBr): 3390, 3200, 3060, 2920, 2850, 1625,1578, 1555, 1519, 1509, 1489, 1465, 1452, 1435, 1395, 1358, 1282, 1255,1192, 1085, 1006, 880, 832, 762, 712; NMR(CDCL): 7.90(1H,d,J=5.5 Hz),7.60-7.15(4H,m), 7.40(1H,d,J=5.5 Hz), 3.45-3.15(2H,br), 3.00(3H,s),2.44(3H,s), 2.38(3H,s)

3-Amino-5-methyl-2-(3-methylphenyl)imidazo[1,2-a]thieno[3,2-c]pyridine(Compound 242)

m.p.: 165.0-166.0° C.; IR(KBr): 3420, 3340, 3080, 2910, 1630, 1606,1530, 1488, 1446, 1410, 1372, 1290, 1254, 1210, 1170, 1096, 1040, 892,790, 710; NMR(CDCL): 7.93(1H,d,J=5.0 Hz), 7.80-7.00(5H,m), 6.72(1H,s),3.46(2H,brs), 2.93(3H,s), 2.41(3H,s)

3-Amino-5-methyl-2-(2-trifluoromethylphenyl)imidazo[1,2-a]thieno[3,2-c]pyridine(Compound 244)

m.p.: 194.0-195.0° C.; IR(KBr): 3380, 3320, 3070, 1630, 1580, 1536,1490, 1473, 1450, 1440, 1405, 1378, 1312, 1295, 1268, 1240, 1190, 1163,1140, 1100, 1050, 1030, 1010, 990, 968, 880, 818, 770, 700; NMR(CDCL):8.10-7.90(1H,m), 7.98(1H,d,J=5.8 Hz), 7.90-7.50(3H,m), 7.48(1H,d,J=5.8Hz), 7.08(1H,s), 2.68(3H,s)

3-Amino-2-(2-methoxyphenyl)-5-methylimidazo[1,2-a]thieno[3,2-c]pyridine(Compound 245)

m.p.: 135.0-136.0° C.; IR(KBr): 3410, 3100, 2930, 2830, 1630, 1568,1532, 1492, 1463, 1456, 1434, 1386, 1372, 1280, 1240, 1178, 1120, 1068,1016, 884, 810, 752, 708; NMR(CDCL): 7.85(1H,d,J=5.0 Hz),7.74(1H,dd,J=2.0 Hz,7.0 Hz), 7.40-6.83(4H,m), 6.70(1H,s), 3.84(3H,s),3.52(2H,br), 2.96(3H,s)

3-Amino-2-(4-chloro-2-methylphenyl)-5-methylimidazo[1,2-a]thieno[3,2-c]pyridine(Compound 248)

m.p.: 206.0-207.0° C.; IR(KBr): 3370, 3150, 1630, 1579, 1530, 1480,1410, 1385, 1370, 1245, 1205, 1173, 1090, 1070, 1010, 862, 810, 700;NMR(CDCL+DMSO): 7.75(1H,d,J=6.0 Hz), 7.42(1H,d,J=6.0 Hz),7.40(1H,d,J=8.0 Hz), 7.40-7.10(2H,m), 6.85(3H,s), 3.90(2H,brs),3.05(3H,s), 2.39(3H,s)

3-Amino-5-methyl-2-(2-thienyl)imidazo[1,2-a]thieno[3,2-c]pyridine(Compound 249)

m.p.: 185.0-186.0° C.; IR(KBr): 3400, 3050, 1630, 1580, 1528, 1468,1434, 1402, 1372, 1300, 1256, 1200, 1172, 1080, 1034, 876, 830, 780,708, 680; NMR(DMSO): 7.73(1H,d,J=5.0 Hz), 7.58(1H,d,J=4.0 Hz),7.48(1H,d,J=5.0 Hz), 7.29(1H,d,J=5.0 Hz), 7.03(1H,dd,J=4.0 Hz,5.0 Hz),6.81(1H,s), 3.40(2H,brs), 2.95(3H,s)

3-Amino-2-(3-methyl-2-thienyl)imidazo[1,2-a]thieno[3,2-c]pyridine(Compound 250)

m.p.: 164.5-165.5° C.; IR(KBr): 3400, 3280, 3060, 1626, 1510, 1472,1402, 1384, 1342, 1276, 1252; 1190, 1168, 1148, 1012, 980, 948, 830,790, 716; NMR(CDCL): 7.90(1H,d,J=5.0 Hz), 7.78(1H,d,J=7.0 Hz),7.44(1H,d,J=5.0 Hz), 7.24(1H,d,J=5.0 Hz), 7.10(1H,d,J=7.0 Hz),6.89(1H,d,J=5.0 Hz), 3.42(2H,brs), 2.38(3H,s)

3-Amino-2-(2-methyl-3-thienyl)imidazo[1,2-a]thieno[3,2-c]pyridine(Compound 254)

m.p.: 161.0-162.0° C.; IR(KBr): 3430, 3270, 3100, 1638, 1622, 1604,1544, 1516, 1492, 1478, 1448, 1410, 1330, 1268, 1198, 1152, 1080, 952,860, 814, 768, 702; NMR(CDCL): 7.91(1H,d,J=5.0 Hz), 7.81 (1H,d,J=7.0Hz), 7.47(1H,d,J=5.0 Hz), 7.30-7.05(3H,m), 3.30(2H,brs), 2.58(3H,s)3-Amino-5-methyl-2-(2-methyl-3-thienyl)imidazo[1,2-a]thieno[3,2-c]pyridine(Compound 255)

m.p.: 139.0-140.0° C.; IR(KBr): 3375, 3250, 3160, 3080, 2910, 1630,1594, 1532, 1510, 1472, 1450, 1438, 1408, 1382, 1308, 1250, 1212, 1158,1000, 880, 816, 696, 675; NMR(CDCL): 7.88(1H,d,J=5.5 Hz),7.38(1H,d,J=5.5 Hz), 7.15(2H,s), 6.78(1H,brs), 3.35(2H,brs), 2.97(3H,s),2.55(3H,s)

3-Amino-2-(2,5-dimethyl-3-thienyl)imidazo[1,2-a]thieno[3,2-c]pyridine(Compound 264)

m.p.: 142.0-143.0° C.; IR(KBr): 3375, 3260, 3175, 3075, 2900, 1625,1540, 1515, 1475, 1435, 1404, 1391, 1375, 1338, 1322, 1246, 1192, 1165,1149, 1135, 1085, 950, 818, 765, 703; NMR(CDCL): 7.95(1H,d,J=5.5 Hz),7.84(1H,d,J=7.0 Hz), 7.50(1H,d,J=5.5 Hz), 7.15(1H,d,J=7.0 Hz),6.89(1H,brs), 3.35(2H,brs), 2.53(3H,s), 2.47(3H,s)

3-Amino-2-1-methyl-2-pyrrolyl)imidazo[1,2-a]thieno[3,2-c]pyridine(Compound 275)

m.p.: 140.0-141.0° C.; IR(KBr): 3380, 3070, 1622, 1490, 1470, 1404,1342, 1300, 1170, 1148, 1090, 1052, 984, 952, 796, 710; NMR(CDCL):7.84(1H,d,J=5.0 Hz), 7.68(1H,d,J=7.0 Hz), 7.41(1H,d,J=5.0 Hz),7.02(1H,d,J=7.0 Hz), 6.70(1H,t,J=2.0 Hz), 6.37-6.10(2H,m), 3.80(3H,s),3.49(2H,brs)

3-Amino-2-(2-methylphenyl)furo[3,2-c]imidazo[1,2-a]pyridine (Compound276)

m.p.: 151.0-152.0° C.(dec.); IR(KBr): 3400, 3270, 3100, 1638, 1592,1504, 1490, 1398, 1360, 1268, 1248, 1176, 1130, 1058, 1030, 990, 890,730; NMR(CDCL): 7.89(1H,d,J=7.0 Hz), 7.67(1H,d,J=2.0 Hz),7.56-7.20(5H,m), 7.10(1H,d,J=7.0 Hz), 3.28(2H,brs), 2.40(3H,s)

3-Amino-2-(2-methyl-3-thienyl)furo[3,2-c]imidazo[1,2-a]pyridine(Compound 280)

m.p.: 146.5-147.0° C.; IR(KBr): 3400, 3300, 3190, 3140, 2920, 1640,1618, 1532, 1507, 1440, 1402, 1332, 1275, 1250, 1193, 1165, 1130, 1059,892, 859, 730; NMR(CDCL): 7.90(1H,d,J=7.0 Hz), 7.70(1H,d,J=2.0 Hz),7.32-7.03(4H,m), 3.26(2H,brs), 2.60(3H,s)

3-Amino-2-(2,5-dimethyl-3-furyl)furo[3,2-c]imidazo[1,2-a]pyridine(Compound 288)

m.p.: 145.5-146.0° C.; IR(KBr): 3450, 3420, 3110, 3075, 2920, 1650,1638, 1597, 1568, 1510, 1445, 1404, 1332, 1279, 1258, 1222, 1210, 1180,1138, 1118, 1064, 995, 980, 924, 892, 800, 752, 730; NMR(CDCL):7.80(1H,d,J=7.0 Hz), 7.60(1H,d,J=2.0 Hz), 7.28-7.14(1H,m),6.99(1H,d,J=7.0 Hz), 6.25(1H,brs), 3.21(2H,brs), 2.52(3H,s), 2.30(3H,s)

3-Amino-7-methyl-2-(2-methylphenyl)imidazo[1,2-a]pyrrolo[3,2-c]pyridine(Compound 291) hydrochloride

m.p.: 219.0° C.(sublimation); IR(KBr): 3360, 3260, 3110, 3070, 2950,2860, 2770, 2700, 1665, 1560, 1538, 1495, 1460, 1425, 1380, 1290, 1252,1212, 1090, 1040, 750; NMR(DMSO): 8.42(1H,d,J=7.0 Hz), 7.73(1H,d,J=7.0Hz), 7.95-7.30(4H,m), 7.58(1H,d,J=3.0 Hz), 7.26(1H,d,J=3.0 Hz),3.98(3H,s), 2.41(3H,s)

3-Amino-7-benzyl-2-(2-methylphenyl)imidazo[1,2-a]pyrrolo[3,2-c]pyridine(Compound 292) hydrochloride

m.p.: 225.0° C.(dec.); IR(KBr): 3360, 3120, 3060, 2650, 1660, 1630,1490, 1445, 1378, 1340, 1300, 1259, 1210, 815, 760, 740, 695; NMR(DMSO):8.42(1H,d,J=7.6 Hz), 7.79(1H,d,J=7.6 Hz), 7.76(1H,d,J=3.0 Hz),7.60-7.10(10H,m), 5.63(2H,s), 2.40(3H,s)

3-Amino-5-methyl-2-(2-methylphenyl)imidazo[1,2-a]thieno[3,4-c]pyridine(Compound 303)

m.p.: 154.0-154.5° C.; IR(KBr): 3390, 3170, 3100, 3050, 3010, 2960,2920, 1645, 1610, 1580, 1530, 1488, 1455, 1430, 1403, 1382, 1366, 1310,1292, 1270, 1220, 1190, 1095, 1038, 960, 858, 835, 825, 770, 750, 730;NMR(CDCL): 7.98(1H,d,J=3.0 Hz), 7.40-7.00(5H,m), 6.36(1H,s),3.29(2H,brs), 2.70(3H,s), 2.32(3H,s)

3-Amino-2-(2-methylphenyl)imidazo[1,2-a]thieno[2,3-c]pyridine (Compound310)

m.p.: 133.5-134.0° C.; Analysis Calcd. for C₁₆ H₁₃ N₃ S; : C 68.79%, H4.69%, N 15.04%; Found: C 68.74%, H 4.87%, N 14.79%; MS(EI)m/z: 279(M⁺),263, 150, 135, 83; HRMS(EI)m/z: 279.08233(Calcd. for: C₁₆ H₁₃ N₃ S;279.3588); IR(KBr): 3350, 3150, 2920, 1630, 1575, 1510, 1490, 1450,1412, 1373, 1306, 1262, 940, 850, 762, 726; NMR(CDCL): 7.78(1H,d,J=7.0Hz), 7.50-7.00(7H,m), 3.28(2H,brs), 2.37(3H,s)

3-Amino-5-methyl-2-(2-methylphenyl)imidazo[1,2-a]thieno[2,3-c]pyridine(Compound 311)

m.p.: 179.5-180.0° C.; IR(KBr): 3380, 3270, 3180, 1632, 1572, 1532,1490, 1443, 1427, 1385, 1360, 1338, 1298, 1278, 1247, 1200, 1032, 930,820, 764; NMR(CDCL): 7.33-7.03(6H,m), 6.66(1H,s), 3.25(2H,brs),2.90(3H,s), 2.30(3H,s)

3-Amino-8-methyl-2-(2-methylphenyl)imidazo[1,2-a]thieno[2,3-c]pyridine(Compound 312)

m.p.: 153.0-153.5° C.; IR(KBr): 3330, 3250, 3160, 2900, 1626, 1570,1516, 1490, 1448, 1422, 1373, 1298, 1262, 1198, 1170, 1038, 912, 822,760, 720; NMR(CDCL): 7.83(1H,d,J=7.0 Hz), 7.63-7.20(4H,m),7.00(1H,d,J=7.0 Hz), 6.96(1H,s), 3.36(2H,brs), 2.60(3H,s), 2.38(3H,s)

3-Amino-2-(2-methylphenyl)furo[2,3-c]imidazo[1,2-a]pyridine (Compound318)

m.p.: 65.5-67.0° C.; IR(KBr): 3400, 3300, 3120, 1620, 1584, 1532, 1490,1438, 1388, 1363, 1270, 1250, 1159, 1118, 1002, 888, 766, 720;NMR(CDCL): 7.86(1H,d,J=7.0 Hz), 7.70(1H,d,J=2.0 Hz), 7.55-7.20(4H,m),6.97(1H,d,J=7.0 Hz), 6.80(1H,d,J=2.0 Hz), 3.46(2H,brs), 2.40(3H,s)

3-Amino-2-(2-methylphenyl)-5,6-dihydroimidazo[1,2-a]thieno[2,3-c]pyridine(Compound 323)

IR(KBr): 3400, 3300, 3050, 2920, 1665, 1625, 1560, 1480, 1432, 1380,1340, 1220, 1178, 1134, 1090, 1040, 945, 870, 750, 720; NMR(CDCL):7.40-7.10(5H,m), 6.89(1H,d,J=5.0 Hz), 4.02(2H,t,J=7.0 Hz),3.30-3.00(2H,br), 3.10(2H,t,J=7.0 Hz), 2.39(3H,s)

EXAMPLE 4

3-Acetylamino-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline (Compound112)

To a solution of 1.5 g of3-amino-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline(Compound 3) in 20ml of ethanol was added 3.0 ml of acetic anhydride. After 1 hour,precipitated crude crystalline was collected by filtration andrecrystallized from ethanol to give 1.5 g of the title compound as awhite powder.

m.p.: >270.0° C.; IR(KBr): 3090, 2940, 2800, 1690, 1645, 1619, 1598,1515, 1460, 1405, 1384, 1284, 782; NMR(DMSO): 8.28-8.08(1H,m),7.81-7.05(9H,m), 2.47(3H,s), 2.20(3H,s)

EXAMPLE 5

Compounds obtained in the same manner as in Example 4 are collectivelyshown below.

3-Acetylamino-2-(2-fluorophenyl)imidazo[2,1-a]isoquinoline (Compound111)

IR(KBr): 3160, 3090, 2950, 2800, 1695, 1645, 1629, 1603, 1580, 1515,1490, 1459, 1410, 1382, 1370, 1319, 1285, 1272, 1224, 1130, 1095, 1034,1007, 954, 932, 900, 850, 810, 785, 748, 700; NMR(DMSO):8.70-8.45(1H,m), 8.20-7.05(10H,m), 2.19(3H,s)

3-(3-Chloropropionylamino)-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline(Compound 124)

m.p.: 223.0° C.(sublimation); IR(KBr): 3150, 3070, 3020, 2940, 2870,2760, 1690, 1645, 1617, 1596, 1517, 1458, 1438, 1421, 1403, 1380, 1300,1252, 1215, 980, 928, 900, 770, 718; NMR(DMSO): 10.25(1H,brs),8.69-8.42(1H,m), 8.04-7.20(9H,m), 4.00(2H,t,J=7.0 Hz), 3.00(2H,t,J=7.0Hz), 2.46(3H,s)

2-(2-Methylphenyl)-3-[3-(methylthio)propionylamino]imidazo[2,1-a]isoquinoline(Compound 125)

m.p.: 219.0-220.0° C.; IR(KBr): 3090, 2940, 1699, 1643, 1619, 1595,1515, 1490, 1459, 1425, 1400, 1381, 1286, 1244, 1230, 1140, 900, 775,726; NMR(DMSO): 10.2(1H,brs), 8.69-8.40(1H,m), 8.14-7.11(9H,m),2.80(4H,s), 2.43(3H,s), 2.12(3H,s)

3-[(3-Carboxypropionyl)amino]-2-(2,4-dimethylphenyl)imidazo[2,1-a]isoquinoline(Compound 127)

IR(KBr): 3210, 2940, 1750, 1660, 1602, 1516, 1459, 1382, 1260, 1240,1165, 990, 955, 900, 817, 780; NMR(DMSO): 12.9-11.7(1H,br),10.1(1H,brs), 8.65-8.33(1H,m), 8.04-6.90(8H,m), 2.65(4H,s), 2.38(3H,s),2.32(3H,s)

3-Hexanoylamino-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline (Compound128)

IR(KBr): 3150, 3080, 2940, 2870, 1698, 1643, 1618, 1597, 1514, 1490,1458, 1402, 1380, 1312, 1288, 1247, 1180, 1105, 960, 898, 773, 722;NMR(DMSO): 9.90(1H,s), 8.70-8.43(1H,m), 8.05-7.15(9H,m), 2.40(3H,s),1.95-0.70(11H,m)

3-(Methoxyfumaroylamino)-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline(Compound 129)

m.p.: 254.0-256.0° C.(dec.); IR(KBr): 3140, 3080, 2960, 2800, 1735,1691, 1640, 1617, 1598, 1515, 1458, 1400, 1380, 1328, 1310, 1202-1185,1163, 990, 778, 755; NMR(DMSO): 10.65(1H,s), 8.61-8.39(1H,m),8.00-7.15(10H,m), 6.77(1H,d,J=16.0 Hz), 3.77(3H,s), 2.39(3H,s)

3-(p-Anisoylamino)-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline(Compound 131)

m.p.: >270.0° C.; IR(KBr): 3075, 2950, 2860, 1664, 1610, 1590, 1520,1498, 1460, 1382, 1318, 1287, 1257, 1180, 1030, 845, 780, 725;NMR(DMSO): 10.37(1H,brs), 8.66-8.37(1H,m), 8.17-6.90(13H,m), 3.85(3H,s),2.44(3H,s)

2-(2-Methylphenyl)-3-(2-thenoylamino)imidazo[2,1-a]isoquinoline(Compound 132)

m.p.: >270.0° C.; IR(KBr): 3080, 2925, 1660, 1615, 1592, 1525, 1490,1460, 1422, 1400, 1383, 1359, 1290, 1100, 788, 720; NMR(DMSO):10.6(1H,brs), 8.70-8.40(1H,m), 8.16-7.10(12H,m), 2.46(3H,s)

3-[(3-Methyl-2-benz[b]furoyl)amino]-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline(Compound 133)

m.p.: >280.0° C.; IR(KBr): 3230, 3150, 3070, 2940, 1673, 1609, 1590,1500, 1453, 1420, 1400, 1380, 1315, 1294, 1268, 1190, 1145, 1095, 910,833, 768; NMR(DMSO): 10.73(1H,brs), 8.36-8.10(1H,m), 7.91-7.08(13H,m),2.67(3H,s), 2.54(3H,s)

3-Ethoxycarbonylamino-2-(2-methylpheny)imidazo[1,2-a]thieno[3,2-c]pyridine(Compound 355)

m.p.: 204.0° C.(sublimation); IR(KBr): 3080, 2970, 2900, 1722, 1629,1618, 1594, 1475, 1409, 1390, 1349, 1299, 1241, 1210, 1182, 1095, 1060,1010, 957, 760, 708; NMR(CDCL): 7.92(1H,d,J=5.4 Hz), 7.68(1H,d,J=6.6Hz), 7.50(1H,d,J=5.4 Hz), 7.40-7.00(6H,m), 4.18(2H,q,J=7.0 Hz),2.30(3H,s), 1.21(3H,t,J=7.0 Hz)

EXAMPLE 6

3-(N-Acetyl-N-propylamino)-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline(Compound 138) hydrochloride

A solution of 6 g of3-acetylamino-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline(Compound 112)in 250 ml of dry N,N-dimethylformamide was added dropwise to a solutionof 0.9 g of sodium hydride in oil (prewashed with hexane) in 50 ml ofdry N,N-dimethylformamide over 30 minutes under dry argon atmosphere atroom temperature. After the mixture was stirred for further 1 hour, 2.2ml of propyl bromide was added dropwise. When addition was complete, themixture was stirred at room temperature for 2 hours. The reactionmixture was poured into water and extracted with ethyl acetate. Theextract was washed with water and saturated saline, and dried overanhydrous magnesium sulfate. The drying agent was removed by filtration,and the solvent was removed under reduced pressure. The residue waspurified by column chromatography on silica gel to give 11.0 g of3-(N-acetyl-N-propylamino)-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline(Compound 138) as a brown viscous material. To a solution of 3.0 g ofthe product in 100 ml of ether was added a saturated solution ofhydrogen chloride in ether, and precipitated crystalline was collectedby filtration. Recrystallization from ether/chloroform gave 2.7 g of thetitle compound as a white powder.

m.p.: 174.5-177.0° C.; Analysis Calcd. for C₂₃ H₂₃ N₃.HCl.0.3H₂ O; : C69.18%, H 6.21%, N 10.52%; Found: C 69.30%, H 6.08%, N 10.54%; IR(KBr):3075, 3040, 2980, 2940, 2890, 2500, 2260, 1683, 1630, 1543, 1498, 1460,1430, 1397, 1332, 1300, 1243, 1148, 810, 750; NMR(DMSO):9.48-9.10(1H,m), 8.50(1H,d,J=8.0 Hz), 8.36-7.78(4H,m), 7.60-7.30(4H,m),3.80-3.10(2H,m), 2.45(3H,s), 2.38,2.00(3H,each s), 1.62-1.02(2H,m),0.65(3H,t,J=7.0 Hz) MS(EI)m/z: 357(M-HCl)⁺, 314, 272, 245, 128;

EXAMPLE 7

Compounds obtained in the same manner as in Example 6 are collectivelyshown below.

3-[N-Acetyl-N-(ethoxycarbonylmethyl)amino]-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline(Compound 134)

m.p.: 127.0-128.0° C.; IR(KBr): 3070, 3000, 2950, 2875, 1752, 1692,1640, 1610, 1585, 1565, 1520, 1490, 1458, 1401, 1379, 1335, 1269, 1238,1205, 1165, 1140, 1094, 1030, 980, 895, 800, 769, 729, 705; NMR(CDCL):8.80-8.60(1H,m), 8.41(1H,d,J=7.0 Hz), 7.80-7.50(3H,m), 7.40-7.10(5H,m),4.81(1H,d,J=17.0 Hz), 4.19(2H,q,J=7.0 Hz), 3.52(1H,d,J=17.0 Hz),2.40(3H,s),1.95(3H,s), 1.25(3H,t,J=7.0 Hz)

3-[N-Acetyl-N-(N,N-diethylcarbamoylmethyl)amino]-2-(3-ethyl-2-thienyl)imidazo[2,1-a]isoquinoline(Compound 135)

IR(Neat): 3080, 2980, 2940, 2880, 1690, 1656, 1610, 1582, 1520, 1480,1452, 1371, 1330, 1260, 1238, 1215, 1144, 1072, 1031, 980, 950, 908,800-780, 740; NMR(CDCL): 8.92(1H,d,J=7.0 Hz), 8.86-8.60(1H,m),7.87-7.51(3H,m), 7.33-7.00(3H,m), 5.21(1H,d,J=16.0 Hz), 3.58(1H,d,J=16.0Hz), 3.57-3.00(6H,m), 1.93(3H,s), 1.48-0.98(9H,m)

3-[N-Acetyl-N-(2-methoxyethyl)amino]-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline(Compound 136) hydrochloride

m.p.: 104.0-107.0° C.; IR(KBr): 3100-3000, 2950-2800, 2750-2300, 1684,1665, 1629, 1545, 1498, 1455, 1429, 1400, 1385, 1338, 1272, 1245, 1235,1196, 1120, 1100, 1008, 805-740; NMR(CDCL): 10.00-9.65(1H,m),8.25-7.60(5H,m), 7.50-7.20(4H,m), 4.60-280(4H,m), 3.11(3H,s), 2.55,2.40(3H,each s), 2.48, 2.00(3H,each s)

3-(N-Acetyl-N-propylamino)-2-(2-fluorophenyl)imidazo[2,1-a]isoquinoline(Compound 137)

IR(KBr): 3080, 2960, 2870, 1680, 1636, 1610, 1570, 1523, 1452, 1380,1348, 1300, 1254, 1220, 1150, 800, 760, 740; NMR(CDCL): 8.90-8.60(1H,m),8.10-6.90(9H,m), 4.20-2.85(2H,m), 1.98(3H,s), 1.80-1.10(2H,m),0.78(3H,t,J=7.0 Hz)

3-(N-Acetyl-N-propylamino)-9-methoxy-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline(Compound 141)

IR(KBr): 3070, 2960, 2940, 2880, 1680, 1635, 1618, 1518, 1500, 1440,1380, 1340, 1290, 1230, 1140, 1028, 824; NMR(CDCL): 8.13(1H,d,J=3.0 Hz),7.70(1H,d,J=8.0 Hz), 7.63(1H,d,J=7.0 Hz), 7.43-7.07(6H,m),4.11-2.90(2H,m), 4.00(3H,s), 2.46(3H,s), 1.98(3H,s), 1.78-1.10(2H,m),0.78(3H,t,J=7.0 Hz)

3-(N-Acetyl-N-propylamino)-2-(3-methylphenyl)imidazo[2,1-a]isoquinoline(Compound 143)

IR(KBr): 3070, 2980, 2930, 2880, 1670, 1640, 1612, 1570, 1522, 1486,1458, 1420, 1396, 1375, 1349, 1295, 1256, 1240, 1215, 1155, 1072, 1035,977, 798, 749, 728, 702; NMR(CDCL): 8.92-8.67(1H,m), 8.00-7.00(9H,m),4.25-3.18(2H,m), 2.42(3H,s), 1.90-1.22(2H,m), 1.89(3H,s),0.83(3H,t,J=7.0 Hz)

3-(N-Acetyl-N-propylamino)-2-(3-methyl-2-thienyl)imidazo[2,1-a]isoquinoline(Compound 144)

IR(Neat): 3070, 3010, 2960, 2940, 2880, 1678, 1640, 1610, 1584, 1520,1482, 1456, 1441, 1370, 1335, 1298, 1260, 1240, 1218, 1150, 1070, 1030,960, 934, 890, 832, 790, 748; NMR(CDCL): 8.90-8.60(1H,m),7.84-7.54(4H,m), 7.35-7.19(2H,m), 7.00(1H,d,J=5.0 Hz), 4.29-3.79(1H,m),3.59-3.09(1H,m), 2.71(3H,s), 1.90(3H,s), 1.78-1.10(2H,m),0.83(3H,t,J=7.0 Hz)

3-(N-Acetyl-N-isopropylamino)-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline(Compound 145)

IR(KBr): 3080, 2990, 2950, 2890, 1670, 1640, 1612, 1588, 1568, 1518,1485, 1456, 1370, 1330, 1310, 1238, 1212, 1176, 1132, 1118, 1102, 1088,1040, 956, 925, 892, 796, 782, 740; NMR(CDCL): 8.92-8.58(1H,m),7.88-7.02(9H,m), 5.10-4.56(1H,m), 2.52(3H,s), 2.00(3H,s),0.93(3H,d,J=7.0 Hz), 0.69(3H,d,J=7.0 Hz)

3-(N-Acetyl-N-allylamino)-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline(Compound 146)

IR(Neat): 3080, 3030, 2950, 1675, 1640, 1612, 1590, 1570, 1520, 1485,1456, 1372, 1326, 1240, 1142, 1100, 1046, 980, 928, 896, 740; NMR(CDCL):8.83-8.53(1H,m), 7.88-7.46(4H,m), 7.39-7.02(5H,m), 6.10-5.40(1H,m),5.20-4.74(2H,m), 4.74-4.40(1H,m), 3.93-3.55(1H,m), 2.45(3H,s),1.94(3H,s)

3-(N-Acetyl-N-isopentylamino)-2-(2-ethylphenyl)imidazo[2,1-a]isoquinoline(Compound 148)

IR(Neat): 3090, 2980, 2950, 2890, 1680, 1641, 1612, 1588 ,1568 , 1520,1490, 1458, 1378, 1345, 1295, 1270, 1250, 1233, 1210, 1155, 1100, 1070,1031, 981, 893, 790, 750, 700; NMR(CDCL): 8.88-8.62(1H,m),7.88-7.50(4H,m), 7.40-7.13(5H,m), 4.19-3.70(1H,m), 3.48-2.68(3H,m),2.00(3H,s), 1.60-1.00(3H,m), 1.26(3H,t,J=7.0 Hz), 0.80(3H,d,J=6.0 Hz),0.72(3H,d,J=6.0 Hz)

3-[N-Acetyl-N-(4-methylbenzyl)amino]-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline(Compound 151)

IR(KBr): 3070, 3030, 2940, 1680, 1640, 1612, 1587, 1565, 1519, 1486,1458, 1376, 1333, 1318, 1290, 1250, 1230, 1190, 1100, 1035, 970, 892,790, 730; NMR(CDCL): 8.90-8.60(1H,m), 7.85-7.55(3H,m), 7.45-6.80(10H,m),5.32(1H,d,J=13.0 Hz), 4.10(1H,d,J=13.0 Hz), 2.34(3H,s), 2.22(3H,s),1.95(3H,s) (hydrochloride m.p.: 126.0-128.0° C.)

3-[N-Ethyl-N-[3-(methylthio)propionyl]amino]-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline(Compound 152)

IR(Neat): 3080, 2990, 2940, 1678, 1640, 1612, 1588, 1568, 1520, 1488,1458, 1377, 1350, 1258, 1217, 1150, 1128, 1000, 1045, 1022, 980, 930,893, 790, 750-730, 700; NMR(CDCL): 8.87-8.55(1H,m), 7.89-7.49(4H,m),7.37-7.02(5H,m), 4.23-3.18(2H,m), 2.98-2.62(2H,m), 2.57-2.17(2H,m),2.48(3H,s), 1.94(3H,s), 1.05(3H,t,J=7.0 Hz)

2-(2,4-Dimethylphenyl)-3-succinylaminoimidazo[2,1-a]isoquinoline(Compound 154)

m.p.: 233.0-233.5° C.; IR(KBr): 2940, 1728, 1645, 1623, 1600, 1520,1460, 1427, 1380, 1330, 1169, 780; NMR(CDCL): 8.83-8.53(1H,m),7.72-6.84(8H,m), 2.81(4H,s), 2.36(3H,s), 2.32(3H,s)

EXAMPLE 8

3-(N-Ethyl-N-propylamino)-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline(Compound 207) hydrochloride

A solution of 4.0 g of3-(N-acetyl-N-propylamino)-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline(Compound138) in 30 ml of dry tetrahydrofuran was added dropwise to a solution of0.7 g of lithium aluminum hydride in 20 ml of dry tetrahydrofuran over aperiod of 30 minutes. The mixture was stirred at room temperature for 4hours. After excessive lithium aluminum hydride was decomposed by theaddition of hydrous ether, the mixture was dried over anhydrousmagnesium sulfate. The drying agent was removed by filtration, and thesolvent was removed under reduced pressure. The residue was purified bycolumn chromatography on silica gel to give 3.5 g of3-(N-ethyl-N-propylamino)-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline(Compound207) as a yellow oily material. To a solution of 3.5 g of the product in100 ml of ether was added a saturated solution of hydrogen chloride inether, and precipitated crystalline was collected by filtration.Recrystallization from ether/chloroform gave 3.0 g of the title compoundas a white powder.

m.p.: 168.5-172.5° C.; Analysis Calcd. for C₂₃ H₂₅ N₃.HCl.0.2H₂ O; : C72.03%, H 6.94%, N 10.96%; Found: C 72.04%, H 6.88%, N 10.93%; IR(KBr):3050, 2980, 2950, 2880, 2540, 1655, 1620, 1545, 1500, 1460, 1420, 1388,1328, 1283, 1236, 1096, 808, 750; NMR(DMSO): 9.55-9.22(1H,m),8.70-7.85(5H,m), 7.70-7.37(4H,m), 3.09(2H,q,J=7.0 Hz), 2.92(2H,t,J=7.0Hz), 2.43(3H,s), 1.68-0.93(2H,m), 1.10(3H,t,J=7.0 Hz), 0.80(3H,t,J=7.0Hz); MS(EI)m/z: 343(M-HCl)⁺, 314, 300, 245, 128

EXAMPLE 9

2-(2-Methylphenyl)-3-[(1-phenylethyl)amino]imidazo[2,1-a]isoquinoline(Compound 192)

A solution of 5 g of3-amino-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline (Compound 3) in 30ml of dry N,N-dimethylformamide was added dropwise to a solution of 1.2g of sodium hydride in oil (prewashed with hexane) in 10 ml of dryN,N-dimethylformamide over 30 minutes under dry argon atmosphere at roomtemperature. After the mixture was stirred for further 1 hour, asolution of 4.1 g of (1-bromoethyl)benzene in 30 ml of dryN,N-dimethylformamide was added dropwise. When addition was complete,the mixture was stirred at room temperature for 1 hour. The solution waspoured into water and extracted with ethyl acetate. The extract waswashed with water and saturated saline, and dried over anhydrousmagnesium sulfate. The drying agent was removed by filtration, and thesolvent was removed under reduced pressure. The residue was purified bycolumn chromatography on silica gel, and recrystallized frombenzene/hexane to give 5.3 g of the title compound as colorless needles.

m.p.: 160.5-161.5° C.; IR(KBr): 3350, 3060, 3020, 2960, 2920, 1608,1580, 1558, 1517, 1480, 1455, 1390, 1368, 1264, 1230, 1210, 1183, 1156,1125, 1090, 1078, 1008, 800, 748, 720, 690; NMR(CDCL): 8.76-8.55(1H,m),7.95(1H,d,J=7.5 Hz), 7.67-7.09(12H,m), 6.99(1H,d,J=7.5 Hz),4.30-3.85(1H,m), 3.48-3.15(1H,m), 2.28(3H,s), 1.28(3H,d,J=6.5 Hz)

EXAMPLE 10

A solution of 3.0 g of3-amino-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline (Compound 3) in 30ml of dry N,N-dimethylformamide was added dropwise to a solution of 0.9g of sodium hydride in oil (prewashed with hexane) in 50 ml of dryN,N-dimethylformamide over 30 minutes under dry argon atmosphere at roomtemperature. After the mixture was stirred for further 1 hour, 1.0 ml ofallyl bromide was added dropwise. The mixture was stirred at roomtemperature for 2 hours, and then at 50° C. for 16 hours. The solutionwas poured into water, and extracted with ethyl acetate. The extract waswashed with water and saturated saline, and dried over anhydrousmagnesium sulfate. The drying agent was removed by filtration, and thesolvent was removed under reduced pressure. The residue was purified bycolumn chromatography on silica gel to give 1.5 g of3-diallylamino-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline(Compound223) as a brown oily material. The chromatography successively gave 0.5g of 3-allylamino-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline(Compound221) as a brown oily material.

Physico-chemical data of3-diallylamino-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline(Compound223) is shown below.

IR(Neat): 3090, 3030, 3000, 2940, 2850, 1645, 1611, 1583, 1560, 1520,1482, 1458, 1420, 1375, 1342, 1230, 1189, 1158, 1091, 990, 921, 790,750-730, 700; NMR(CDCL): 8.84-8.55(1H,m), 8.00(1H,d,J=7.0 Hz),7.83-7.20(7H,m), 7.02(1H,d,J=7.0 Hz), 6.20-5.44(2H,m), 5.27-4.83(4H,m),3.55(4H,d,J=5.0 Hz), 2.33(3H,s); (hydrochloride m.p.: 167.0-168.0° C.)

Physico-chemical data of3-allylamino-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline(Compound 221)is shown below.

IR(Neat): 3250, 3075, 2990, 2940, 2860, 1643, 1610, 1585, 1519, 1482,1458, 1419, 1373, 1330, 1244, 1186, 1140, 1093, 1045, 990, 920, 896,789, 750-730; NMR(CDCL): 8.75-8.46(1H,m), 7.86(1H,d,J=7.0 Hz),7.68-7.13(7H,m), 6.97(1H,d,J=7.0 Hz), 6.17-5.39(1H,m), 5.28-4.83(2H,m),3.48(2H,d,J=5.0 Hz), 3.43-2.98(1H,brs), 2.40(3H,s) (hydrochloride m.p.:195.0-198.0° C.(dec.))

EXAMPLE 11

Example 10 was repeated except that N,N-diethylchloroacetamide was usedin place of allyl bromide, which gave 3-(N,N-diethylcarbamoylmethyl)amino-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline (Compound 157)as a brown oily material and3-[bis(N,N-diethylcarbamoylmethyl)amino]-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline(Compound 198) as a brown oily material. To a solution of 1.6 g of theformer compound in 50 ml of ether was added a saturated solution ofhydrogen chloride in ether, and precipitated crystalline was collectedby filtration. Recrystallization from ethyl acetate/chloroform gave 1.0g of3-(N,N-diethylcarbamoylmethyl)amino-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline(Compound 157) hydrochloride as a yellow ocher powder.

Physico-chemical data of3-(N,N-diethylcarbamoylmethyl)amino-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline(Compound 157) hydrochloride is shown below.

m.p.: 187.0-190.0° C.; IR(KBr): 3240, 2990, 2950, 2550, 1659, 1570,1550, 1490, 1462, 1388, 1340, 1310, 1270, 1223, 1138, 1100, 895, 800,754; NMR(DMSO): 9.20-8.85(1H,m), 8.78(1H,d,J=7.0 Hz), 8.22-7.63(4H,m),7.55-7.18(4H,m), 3.70(2H,s), 3.32-2.67(4H,m), 2.32(3H,s),0.91(3H,t,J=7.0 Hz). 0.73(3H,t,J=7.0 Hz)

Physico-chemical data of3-[bis(N,N-diethylcarbamoylmethyl)amino]-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline(Compound 198) is shown below.

IR(Neat): 3080, 2990, 2950, 1658, 1640, 1565, 1519, 1456, 1380, 1310,1262, 1220, 1190, 1132, 1098, 1048, 980, 945, 897, 740; NMR(CDCL):8.72-8.51(1H,m), 8.66(1H,d,J=7.0 Hz), 7.82-7.17(7H,m), 7.06(1H,d,J=7.0Hz), 3.93(4H,s), 3.52-2.94(8H,m), 2.32(3H,s), 1.06(12H,t,J=7.0 Hz)

EXAMPLE 12

Example 10 was repeated except that3-amino-7-chloro-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline (Compound5) and ethyl iodide were used in place of3-amino-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline and allyl bromide,which gave7-chloro-3-ethylamino-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline(Compound 159) as yellow needles and7-chloro-3-diethylamino-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline(Compound 199) as colorless needles.

Physico-chemical data of7-chloro-3-diethylamino-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline(Compound 199) is shown below.

m.p.: 102.0-102.5° C.; IR(KBr): 2980, 2860, 1600, 1558, 1512, 1490,1474, 1450, 1370, 1342, 1218, 1088, 900, 788; NMR(CDCL):8.64(1H,dd,J=3.0 Hz,7.0 Hz), 8.19(1H,d,J=7.0 Hz), 7.72-7.18(7H,m),2.97(4H,q,J=7.0 Hz),2.32(3H,s), 1.00(6H,t,J=7.0 Hz)

Physico-chemical data of7-chloro-3-ethylamino-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline(Compound 159) is shown below.

m.p.: 157.0-158.0° C.; IR(KBr): 3270, 2980, 2940, 1638, 1600, 1578,1505, 1472, 1440, 1405, 1370, 1353, 1300, 1260, 1210, 1190, 1160, 1120,1083, 996, 900, 820, 772, 740, 720; NMR(CDCL): 8.60(1H,dd,J=2.0 Hz,7.0Hz), 8.00(1H,d,J=7.0 Hz), 7.67-7.19(7H,m), 3.27-2.98(1H,br),2.98(2H,q,J=7.0 Hz), 2.40(3H,s), 1.07(3H,t,J=7.0 Hz)

EXAMPLE 13

Example 10 was repeated except that3-amino-7-methoxycarbonyl-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline(Compound 51) and methyl iodide were used in place of3-amino-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline and allyl bromide,which gave3-dimethylamino-7-methoxycarbonyl-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline(Compound 197) as a pale yellow powder.

m.p.: 130.0-130.5° C.; IR(KBr): 2950, 2880, 2800, 1713, 1636, 1600,1560, 1492, 1428, 1370, 1307, 1259, 1200, 1110, 1012, 970, 926, 800;NMR(CDCL): 8.92(1H,dd,J=2.0 Hz,7.0 Hz), 8.30(1H,d,J=8.0 Hz),8.20(1H,dd,J=2.0 Hz,8.0 Hz), 7.98(1H,d,J=8.0 Hz), 7.57(1H,t,J=8.0 Hz),7.30(4H,s), 4.00(3H,s), 2.72(6H,s), 2.37(3H,s)

EXAMPLE 14

2-(2-Methylphenyl)-3-piperidinoimidazo[2,1-a]isoquinoline (Compound 217)hydrochloride

To a solution of 3.0 g of3-amino-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline(Compound 3) in 50ml of dry N,N-dimethylformamide was added successively 4.6 g ofpotassium carbonate and 1.6 ml of 1,5-dibromopentane, and the mixturewas stirred at 140° C. for 3 hours. After being cooled, the mixture waspoured into water and extracted with ethyl acetate. The extract waswashed with water and saturated saline, and dried over anhydrousmagnesium sulfate. The drying agent was removed by filtration, and thesolvent was removed under reduced pressure. The residue was purified bycolumn chromatography on silica gel to give 3.7 g of2-(2-methylphenyl)-3-piperidinoimidazo[2,1-a]isoquinoline (Compound 217)as a brown oily material. To a solution of 2.0 g of the product in 80 mlof ether was added a saturated solution of hydrogen chloride in ether,and precipitated crystalline was collected by filtration.Recrystallization from ethyl acetate/petroleum ether gave 1.4 g of thetitle compound as a white powder.

m.p.: 212.0-215.0° C.; Analysis Calcd. for C₂₃ H₂₃ N₃.HCl.0.5H₂ O; : C71.40%, H 6.51%, N 10.86%; Found: C 71.44%, H 6.45%, N 10.94%; IR(KBr):2950, 2850, 2620, 1660, 1622, 1548, 1498, 1450, 1382, 1283, 1130, 905,800, 752; NMR(DMSO): 9.40-9.07(1H,m), 8.45(1H,d,J=7.0 Hz),8.35-7.83(4H,m), 7.70-7.37(4H,m), 3.15-2.70(4H,m), 2.40(3H,s),1.98-1.30(6H,m) MS(EI)m/z: 341(M-HCl)⁺, 284, 257, 245, 128

EXAMPLE 15

2-(2-Methylphenyl)-3-morpholinoimidazo[2,1-a]isoquinoline (Compound 218)hydrochloride

A solution of 5.5 g of3-amino-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline (Compound 3) in 50ml of dry N,N-dimethylformamide was added dropwise to a solution of 1.8g of sodium hydride in oil (prewashed with hexane) in 150 ml of dryN,N-dimethylformamide over 30 minutes under dry argon atmosphere at roomtemperature. After the mixture was stirred for further 1 hour, 3.2 g ofbis(2-chloroethyl)ether was added dropwise. The mixture was stirred atroom temperature for 2 hours, and then at 60° C. for 2 hours. Thereaction mixture was poured into ice water, and extracted with ethylacetate. The extract was washed with water and saturated saline, anddried over anhydrous magnesium sulfate. The drying agent was removed byfiltration, and the solvent was removed under reduced pressure. Theresidue was purified by column chromatography on silica gel to give 2.0g of 2-(2-methylphenyl)-3-morpholinoimidazo[2,1-a]isoquinoline (Compound218) as a yellow oily material. To a solution of 2.0 g of the product in80 ml of ether was added a saturated solution of hydrogen chloride inether. Precipitated crystalline was collected by filtration, and washedwith ethanol to give 1.1 g of the title compound as a yellowish whitepowder.

m.p.: 212.0-217.0° C.; Analysis Calcd. for C₂₂ H₂₁ N₃ O.HCl.0.2H₂ O; : C68.90%, H 5.89%, N 10.96% Found: C 68.87%, H 5.94%, N 10.92% IR(KBr):3040, 2980, 2860, 2740, 2600, 1660, 1625, 1542, 1498, 1459, 1304, 1262,1239, 1202, 1112, 919, 800, 750; NMR(DMSO): 9.38-9.02(1H,m),8.56(1H,d,J=7.0 Hz), 8.41-7.70(4H,m), 7.68-7.38(4H,m), 3.90-3.55(4H,m),3.10-2.77(4H,m), 2.37(3H,s) MS(EI)m/z: 343(M-HCl)⁺, 284, 270, 257, 245,128

EXAMPLE 16

3-(4-Methylbenzylideneamino)-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline(Compound 225)

To a solution of 5 g of3-amino-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline (Compound 3) in 50ml of methanol was added 2.2 g of p-tolualdehyde. After the mixture wasstirred at room temperature for 22 hours, it was poured into water andextracted with ethyl acetate. The extract was washed with water andsaturated saline, and dried over anhydrous magnesium sulfate. The dryingagent was removed by filtration, and the solvent was removed underreduced pressure. The residue was purified by column chromatography onsilica gel, and recrystallization from ethyl acetate/petroleum ethergave 5.4 g of the title compound as yellow crystals.

m.p.: 159.5-160.0° C.; IR(KBr): 3050, 2930, 1603, 1572, 1515, 1480,1458, 1378, 1228, 1173, 1088, 900, 791, 755, 690; NMR(CDCL):8.81-8.58(1H,m), 8.38(1H,d,J=7.0 Hz), 8.22(1H,s), 7.84-7.01(12H,m),2.37(3H,s), 2.27(3H,s)

EXAMPLE 17

3-[(1-Bromo-2-naphthyl)methylideneamino]-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline(Compound 228)

Example 16 was repeated except that 1-bromo-2-naphtoaldehyde was used inplace of p-tolualdehyde, which gave the title compound as a yellowpowder.

m.p.: 250.0-252.0° C.; IR(KBr): 3060, 3020, 2920, 1578, 1515, 1476,1458, 1380, 1328, 1300, 1260, 1230, 1190, 1160, 972, 940, 893, 860, 810,786, 760, 730, 688; NMR(CDCL): 8.94(1H,s), 8.82-8.60(1H,m),8.40(1H,d,J=8.0 Hz), 8.36-8.10(2H,m), 7.87-7.30(11H,m), 7.10(1H,d,J=8.0Hz), 2.30(3H,s)

EXAMPLE 18

2-(2-Methylphenyl)-3-propylideneaminoimidazo[2,1-a]isoquinoline(Compound 224)

Example 16 was repeated except that propylaldehyde was used in place ofp-tolualdehyde, which gave the title compound as a brown oily material.

IR(Neat): 3070, 2980, 1642, 1611, 1516, 1480, 1458, 1380, 1218, 1183,1138, 1090, 1030, 985, 893, 790, 745, 693; NMR(CDCL): 8.84-8.55(1H,m),8.18(1H,d,J=7.0 Hz), 7.78(1H,t,J=4.0 Hz), 7.78-7.19(7H,m),7.02(1H,d,J=7.0 Hz), 2.60-2.08(2H,m), 2.27(3H,s), 1.08(3H,t,J=7.0 Hz)

EXAMPLE 19

2-(2-Ethylphenyl)-3-(4-methylbenzylideneamino)imidazo[2,1-a]isoquinoline(Compound 226)

Example 16 was repeated except that3-amino-2-(2-ethylphenyl)imidazo[2,1-a]isoquinoline (Compound 59) wasused in place of 3-amino-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline,which gave the title compound as a yellow powder.

m.p.: 158.5-159.5° C.; IR(KBr): 2970, 2940, 2880, 1600, 1570, 1515,1476, 1460, 1420, 1380, 1230, 1175, 1088, 970, 900, 812, 790, 765, 742,690; NMR(CDCL): 8.97-8.67(1H,m), 8.46(1H,d,J=7.4.0 Hz), 8.30(1H,s),7.91-7.09(12H,m), 2.68(2H,q,J=7.0 Hz), 2.39(3H,s), 1.10(3H,t,J=7.0 Hz)

EXAMPLE 20

3-(4-Methylbenzylamino)-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline(Compound 194)

To a solution of 4.3 g of3-(4-methylbenzylideneamino)-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline(Compound225) in 50 ml of ethanol was added 0.9 g of sodium borohydride. Afterthe mixture was refluxed for 2 hours, it was poured into water, andextracted with chloroform. The extract was washed with saturated saline,and dried over anhydrous magnesium sulfate. The drying agent was removedby filtration, and the solvent was removed under reduced pressure. Thecrude crystals were recrystallized from petroleum ether/chloroform togive 3.7 g of the title compound as pale yellow needles.

m.p.: 139.0-139.5° C.; IR(KBr): 3360, 3050, 2940, 2860, 1613, 1571,1518, 1459, 1374, 1185, 898, 798, 750, 730; NMR(CDCL): 8.87-8.60(1H,m),7.95(1H,d,J=7.0 Hz), 7.75-6.94(12H,m), 4.13-3.89(2H,m), 3.71-3.44(1H,m),2.37(3H,s), 2.30(3H,s)

EXAMPLE 21

3-Ethylamino-9-methoxy-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline(Compound 167)

To a solution of 5 g of3-amino-9-methoxy-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline (Compound26) in 100 ml of ethanol was added 3.0 ml of acetaldehyde, and themixture was stirred at room temperature for 3 hours. After 3.3 g ofsodium borohydride was added to the mixture and refluxed for 2 hours,the reaction mixture was poured into water, and extracted with ethylacetate. The extract was washed with saturated saline, and dried overanhydrous magnesium sulfate. The drying agent was removed by filtration,and the solvent was removed under reduced pressure. The crude crystalwas recrystallized from petroleum ether/ethyl acetate to give 5 g of thetitle compound as colorless needles.

m.p.: 153.0-154.0° C.; IR(KBr): 3240, 3070, 3040, 2960, 2930, 2900,2850, 1618, 1585, 1568, 1520, 1506, 1473, 1436, 1396, 1379, 1340, 1300,1270, 1223, 1190, 1140, 1050, 1030, 912, 850, 822, 752, 718; NMR(CDCL):8.10(1H,d,J=2.0 Hz), 7.84(1H,d,J=7.0 Hz), 7.63(1H,d,J=8.0 Hz),7.49-6.90(6H,m), 3.97(3H,s),3.28-2.84(1H,br), 2.97(2H,q,J=7.0 Hz),2.40(3H,s), 1.05(3H,t,J=7.0 Hz)

EXAMPLE 22

Compounds obtained in the same manner as in Examples 8, 9, 10 and 21 arecollectively shown below.

2-(2-Methylphenyl)-3-(propoxycarbonylmethyl)aminoimidazo[2,1-a]isoquinoline(Compound 156)

IR(Neat): 3450-3150, 3070, 2480, 2440, 1748, 1672, 1640, 1610,1598-1550, 1520, 1459, 1398, 1378, 1195, 890, 745; NMR(CDCL):8.75-8.54(1H,m), 8.00(1H,d,J=8.0 Hz), 7.75-7.20(7H,m), 7.01(1H,d,J=8.0Hz), 4.00(2H,t,J=6.0 Hz), 3.64(2H,s), 2.40(3H,s), 1.80-1.27(2H,m),0.85(3H,t,J=7.0 Hz)

3-Ethylamino-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline (Compound 158)hydrochloride

m.p.: 236.5-239.5° C.(dec.); IR(KBr): 3160, 3050, 3000, 2940, 2890,2560, 1660, 1625, 1603, 1567, 1550, 1492, 1460, 1424, 1385, 1327, 1305,1237, 1152, 796, 755, 720; NMR(DMSO): 8.94-8.70(1H,m), 8.50(1H,d,J=6.0Hz), 8.14-7.28(8H,m), 2.94(2H,q,J=7.0 Hz), 2.45(3H,s), 1.01(3H,t,J=7.0Hz)

3-Ethylamino-2-(2-methylphenyl)-7-propylimidazo[2,1-a]isoquinoline(Compound 163) hydrochloride

m.p.: 185.0° C.(dec.); IR(KBr): 3170, 3030, 2970, 2940, 2870, 2625,1658, 1618, 1570, 1542, 1486, 1428, 1380, 1343, 1300, 1282, 1240, 1220,1154, 1086, 792, 750; NMR(DMSO): 8.97(1H,dd,J=3.0 Hz,6.0 Hz),8.78(1H,d,J=8.0 Hz), 8.03-7.17(7H,m), 3.10(2H,brt,J=7.0 Hz),2.87(2H,q,J=7.0 Hz), 2.41(3H,s), 1.98-1.38(2H,m), 1.02(6H,t,J=7.0 Hz)

3-Ethylamino-6-methoxymethyl-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline(Compound 164)

m.p.: 115.0-116.5° C.; IR(KBr): 3330, 3080, 2980, 2930, 2900, 2860,2830, 1644, 1610, 1580, 1559, 1523, 1482, 1450, 1395, 1375, 1339, 1278,1240, 1215, 1195, 1155, 1120, 1090, 1060, 1030, 982, 948, 872, 860, 845,825, 755, 715, 700; NMR(CDCL): 8.72-8.50(1H,m), 7.98-7.10(8H,m),4.75(2H,s), 3.47(3H,s), 3.20-2.75(3H,m), 2.40(3H,s), 1.25-0.90(3H,m)

3-Ethylamino-7-hydroxy-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline(Compound 165)

m.p.: 247.0-251.0° C.(dec.); IR(KBr): 3480-3400, 3390, 3100, 2980, 2940,2875, 2375, 1611, 1588, 1565, 1508, 1448, 1381, 1355, 1280, 1252, 1208,1186, 1146, 1015, 949, 785, 741; NMR(DMSO): 10.30(1H,s), 8.10(1H,d,J=7.0Hz), 7.90(1H,brd,J=8.0 Hz), 7.69-7.20(6H,m), 7.00(1H,dd,J=2.0 Hz,8.0Hz), 4.79(1H,brt,J=6.0 Hz), 3.05-2.70(2H,m), 2.40(3H,s), 0.96(3H,t,J=7.0Hz)

3-Ethylamino-6-methoxy-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline(Compound 166)

IR(Neat): 3260, 3070, 2970, 2950, 2880, 1648, 1610, 1568, 1519, 1485,1455, 1372, 1338, 1286, 1228, 1158, 1125, 1100, 1044, 1030, 984, 860;NMR(CDCL): 8.79-8.50(1H,m), 8.15-7.88(1H,m), 7.68-7.08(7H,m),3.90(3H,s), 3.20-2.62(3H,m), 2.39(3H,s), 1.00(3H,t,J=7.0 Hz)(hydrochloride m.p.: 202.0° C.(dec.))

7-Benzyloxy-3-ethylamino-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline(Compound 169)

m.p.: 128.0-129.0° C.; IR(KBr): 3225, 3050, 2950, 2900, 2850, 1610,1585, 1565, 1555, 1520, 1500, 1489, 1450, 1395, 1378, 1332, 1305, 1260,1189, 1176, 1145, 1080, 1060, 1050, 1024, 935, 775, 735, 715; NMR(CDCL):8.30(1H,brd,J=8.0 Hz), 7.90(1H,d,J=7.0 Hz), 7.65-7.20(11H,m),7.00(1H,brd,J=8.0 Hz), 5.25(2H,s), 3.20-2.75(3H,m), 2.40(3H,s),1.07(3H,m)

7-Ethoxycarbonyl-3-ethylamino-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline(Compound 173)

IR(KBr): 3380, 3070, 2980, 2940, 2880, 1718, 1637, 1600, 1557, 1515,1482, 1450, 1370, 1310, 1260, 1210, 1195, 1119, 1022, 925, 790;NMR(CDCL): 8.96(1H,dd,J=2.0 Hz,8.0 Hz), 8.32(1H,d,J=8.0 Hz),8.23(1H,dd,J=2.0 Hz,8.0 Hz), 8.02(1H,d,J=8.0 Hz), 7.62(1H,t,J=8.0 Hz),7.58-7.22(4H,m), 4.50(2H,q,J=7.0 Hz), 3.13-2.70(1H,br), 2.98(2H,q,J=7.0Hz), 2.42(3H,s), 1.47(3H,t,J=7.0 Hz), 1.07(3H,t,J=7.0 Hz)

3-Ethylamino-2-(2-trifluoromethylphenyl)imidazo[2,1-a]isoquinoline(Compound 175)

m.p.: 100.5-101.5° C.; IR(KBr): 3230, 3060, 2980, 2940, 2910, 2860,1639, 1610, 1590, 1570, 1520, 1505, 1483, 1457, 1420, 1390, 1373, 1349,1320, 1275, 1260, 1190, 1168, 1156, 1125, 1115, 1100, 1053, 1032, 980,950, 900, 845, 792, 754, 697; NMR(CDCL): 8.79-8.45(1H,m),8.10-7.30(7H,m), 7.88(1H,d,J=7.6 Hz), 7.01(1H,d,J=7.6 Hz),3.20-2.63(3H,m), 1.02(3H,t,J=7.0 Hz)

3-Ethylamino-6-methoxy-2-(3-methyl-2-thienyl)imidazo[2,1-a]isoquinoline(Compound 176)

m.p.: 142.0-143.0° C.; IR(KBr): 3330, 3090, 3040, 2980, 2950, 2925,2880, 1648, 1590, 1520, 1481, 1471, 1441, 1378, 1341, 1323, 1289, 1230,1214, 1186, 1160, 1135, 1100, 1074, 1020, 990, 968, 861, 830, 773, 732,699; NMR(CDCL): 8.83-8.52(1H,m), 8.20-7.89(1H,m), 7.79-7.48(2H,m),7.41(1H,s), 7.24(1H,d,J=5.0 Hz), 6.96(1H,d,J=5.0 Hz), 3.96(3H,s),3.32-2.76(3H,m), 2.51(3H,s), 1.17(3H,t,J=7.0 Hz)

2-(2-Chloro-3-methyl-4-thienyl)-3-ethylaminoimidazo[2,1-a]isoquinoline(Compound 179)

m.p.: 80.5-81.0° C.; IR(KBr): 3250, 3060, 2960, 2850, 1635, 1608, 1581,1516, 1486, 1443, 1375, 1340, 1230, 1188, 1136, 1004, 960, 892, 776,732, 688; NMR(CDCL): 8.85-8.51(1H,m), 7.92(1H,d,J=7.0 Hz),7.82-7.35(3H,m), 7.21(1H,s), 7.06(1H,d,J=7.0 Hz), 3.31-2.78(3H,m),2.38(3H,s), 1.14(3H,t,J=7.0 Hz)

3-(2-Methoxyethyl)amino-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline(Compound 180) hydrochloride

m.p.: 206.0-208.0° C.(dec.); IR(KBr): 3160, 3050, 2940, 2610, 1662,1625, 1605, 1570, 1550, 1470-1435, 1430, 1330, 1310, 1241, 1200, 1145,1120, 958, 789, 752; NMR(CDCL): 16.10-15.60(1H,br), 9.60-9.38(1H,m),8.55(1H,d,J=8.0 Hz), 7.91-7.62(3H,m), 7.58-7.30(1H,m), 7.42(1H,d,J=8.0Hz), 7.10-6.85(3H,m), 3.48-2.85(4H,m), 3.10(3H,s), 2.40(3H,s)

6-Isopentyl-2-(2-methylphenyl)-3-propylaminoimidazo[2,1-a]isoquinoline(Compound 181)

m.p.: 126.5-127.5° C.; IR(KBr): 3210, 3070, 3025, 2960, 2940, 2875,1640, 1610, 1575, 1520, 1495, 1480, 1465, 1455, 1390, 1368, 1360, 1340,1240, 1154, 760; NMR(CDCL): 8.85-8.55(1H,m), 7.90-7.10(8H,m),3.20-2.70(5H,m), 2.40(3H,s), 1.86-1.25(5H,m), 1.05(6H,d,J=6.0 Hz),0.85(3H,t,J=7.0 Hz)

6-Methoxy-2-(2-methylphenyl)-3-propylaminoimidazo[2,1-a]isoquinoline(Compound 182)

m.p.: 106.0° C.; IR(KBr): 3250, 3070, 3030, 2970, 2930, 2840, 1650,1610, 1589, 1572, 1522, 1482, 1471, 1452, 1412, 1378, 1338, 1308, 1279,1226, 1192, 1152, 1128, 1100, 1068, 990, 863, 790, 758, 715, 702;NMR(CDCL): 8.71-8.45(1H,m), 8.19-7.91(1H,m), 7.71-7.05(7H,m),3.98(3H,s), 3.29-2.59(3H,m), 2.38(3H,s), 1.69-1.10(2H,m),0.86(3H,t,J=7.0 Hz)

3-Isopropylamino-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline(Compound184) hydrochloride

m.p.: 210.0-214.5° C.; IR(KBr): 3450, 3220, 3050, 2990, 2940, 2800,2725, 1663, 1625, 1606, 1570, 1549, 1498, 1460, 1428, 1385, 1370, 1332,1238, 1175, 962, 899, 792, 750; NMR(METH): 8.79-8.37(2H,m),8.37-7.30(8H,m), 3.41-2.94(1H,m), 2.42(3H,s), 1.07(6H,d,J=7.0 Hz)

2-(2-Methylphenyl)-3-[(3-methylthiopropyl)amino]imidazo[2,1-a]isoquinoline(Compound 185)

IR(Neat): 3270, 3070, 2960, 2925, 2860, 1640, 1610, 1568, 1518, 1480,1455, 1374, 1260, 1183, 1135, 1092, 1042, 950, 893, 787, 745, 690;NMR(CDCL): 8.78-8.52(1H,m), 7.92(1H,d,J=7.0 Hz), 7.80-7.40(3H,m),7.28(4H,s), 7.02(1H,d,J=7.0 Hz), 3.31-2.79(3H,m), 2.42(2H,t,J=7.0 Hz),2.38(3H,s), 1.98(3H,s), 1.92-1.50(2H,m)

2-(2-Methylphenyl)-3-[3-(methylsulfinyl)propylamino]imidazo[2,1-a]isoquinoline(Compound 186)

IR(Neat): 3300, 3070, 2960, 2860, 1640, 1610, 1580, 1520, 1480, 1458,1373, 1260, 1216, 1185, 1095, 1020, 940, 890, 790, 745; NMR(CDCL):8.78-8.52(1H,m), 7.92(1H,d,J=7.0 Hz), 7.84-7.20(7H,m), 7.08(1H,d,J=7.0Hz), 3.50-2.80(3H,m), 2.70-2.35(2H,m), 2.40(6H,s), 2.10-1.15(2H,m)

3-Isopentylamino-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline (Compound188)

m.p.: 93.0-93.5° C.; IR(KBr): 3300, 3080, 3040, 2960, 2940, 2880, 1638,1615, 1590, 1576, 1515, 1476, 1460, 1375, 1190, 1092, 900, 795, 772,738; NMR(CDCL): 8.80-8.52(1H,m), 7.90(1H,d,J=7.0 Hz), 7.72-7.19(7H,m),7.00(1H,d,J=7.0 Hz), 3.12-2.73(3H,m), 2.40(3H,s), 1.73-1.05(3H,m),0.80(6H,d,J=6.0 Hz)

3-Isopentylamino-2-(2,4-dimethylphenyl)imidazo[2,1-a]isoquinoline(Compound 189)

IR(Neat): 3250, 3070, 2970, 2940, 2870, 1640, 1612, 1582, 1505, 1485,1456, 1372, 1265, 1237, 1185, 1140, 1094, 894, 786, 745; NMR(CDCL):8.86-8.50(1H,m), 7.88(1H,d,J=7.0 Hz), 7.80-6.82(7H,m), 3.10-2.64(3H,m),2.37(6H,s), 1.55-1.05(3H,m), 0.80(6H,d,J=6.0 Hz); (hydrochloride m.p.:215.0-217.5° C.)

3-Cyclopentylamino-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline(Compound 190)

IR(KBr): 3300, 3080, 2975, 2890, 1640, 1613, 1569, 1521, 1484, 1460,1377, 1186, 1090, 898, 790, 741; NMR(CDCL): 8.78-8.50(1H,m),7.93(1H,d,J=7.0 Hz), 7.70-7.16(7H,m), 6.98(1H,d,J=7.0 Hz),3.60-3.22(1H,m), 3.11-2.73(1H,br), 2.40(3H,s), 1.80-111(8H,m)

3-Hexylamino-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline (Compound 191)

IR(Neat): 3240, 3060, 2960, 2930, 2860, 1635, 1608, 1582-1565, 1518,1480, 1456, 1372, 1260, 1219-1210, 1181, 893, 788, 748; NMR(CDCL):8.82-8.60(1H,m), 7.92(1H,d,J=7.0 Hz), 7.75-7.25(7H,m), 7.06(1H,d,J=7.0Hz), 3.30-2.75(3H,m), 2.40(3H,s), 1.60-0.60(11H,m) (hydrochloride m.p.:172.0-175.0° C.(dec.))

3-[1-Bromo-2-naphthyl)methylamino]-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline(Compound 195)

m.p.: 129.0-130.0° C.; IR(KBr): 3250, 3050, 2940, 2830, 1639, 1610,1570, 1520, 1498, 1483, 1455, 1375, 1325, 1260, 1230, 1213, 1183, 1135,1097, 1026, 965, 896, 865, 815, 783, 760, 715; NMR(CDCL):8.80-8.50(1H,m), 8.33-8.03(1H,m), 7.93(1H,d,J=7.0 Hz), 7.81-7.34(7H,m),7.12-6.87(6H,m), 4.44-4.23(2H,m), 4.18-3.90(1H,m), 2.17(3H,s)

3-[(3-Methyl-2-benz[b]furyl)methylamino]-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline (Compound 196)

IR(KBr): 3390, 3060, 2940, 2860, 1610, 1520, 1480, 1458, 1374, 1328,1265, 1230, 1178, 1117, 790, 740; NMR(CDCL): 8.78-8.54(1H,m),7.90(1H,d,J=8.0 Hz), 7.70-7.03(11H,m), 6.98(1H,d,J=8.0 Hz),4.12(2H,brd,J=5.0 Hz), 3.90-3.57(1H,br), 2.26(3H,s), 1.83(3H,s)

7-Bromo-3-diethylamino-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline(Compound 200)

IR(Neat): 3080, 2980, 2940, 2860, 1635, 1597, 1556, 1515, 1490, 1473,1436, 1371, 1348, 1218, 1104, 897, 780; NMR(CDCL): 8.82-8.45(1H,m),8.30-7.10(8H,m), 2.95(4H,q,J=7.0 Hz), 2.35(3H,s), 0.98(6H,t,J=7.0 Hz);(hydrochloride m.p.: 186.0-187.5° C.)

3-[N-(2-Chloroethyl)-N-ethylamino]-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline(Compound 202) hydrochloride

m.p.: 169.0-169.5° C.; IR(KBr): 3050, 2980, 2920, 2850, 2570, 2350,1740, 1651, 1618, 1540, 1493, 1456, 1419, 1380, 1315, 1280, 1240, 1159,1099, 1030, 894, 804, 747; NMR(DMSO): 9.50-9.19(1H,m), 8.59(1H,d,J=7.0Hz), 8.39-7.75(4H,m), 7.72-7.21(4H,m), 3.70(2H,t,J=5.0 Hz),3.50-2.90(4H,m), 2.40(3H,s), 1.09(3H,t,J=7.0 Hz)

3-[N-Ethyl-N-[2-(N,N-diethylamino)ethyl]amino]-2-(3-ethyl-2-thienyl)imidazo[2,1-a]isoquinoline(Compound 203)

IR(Neat): 3070, 2980, 2940, 2870, 2810, 1638, 1610, 1580, 1520, 1482,1458, 1372, 1345, 1202, 1155, 1068, 905, 890, 788, 735, 698; NMR(CDCL):8.83-8.58(1H,m), 8.12(1H,d,J=7.0 Hz), 7.81-7.44(3H,m), 7.31-6.95(3H,m),3.36-2.29(12H,m), 1.25(3H,t,J=7.0 Hz), 1.02(3H,t,J=7.0 Hz),0.92(6H,t,J=7.0 Hz)

3-[N-Ethyl-N-(2-methoxyethyl)amino]-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline(Compound 205) hydrochloride

m.p.: 156.5-159.0° C.; IR(KBr): 3040, 2990, 2940, 2850, 2575, 2400,2320, 1783-1769, 1655, 1620, 1605, 1541, 1499, 1455, 1420, 1388, 1375,1350, 1330, 1300, 1288, 1238, 1198, 1115, 1110, 1072, 1015, 920-855,808, 765, 751, 725, 695; NMR(CDCL): 10.00-9.72(1H,m), 8.50(1H,d,J=8.0Hz), 8.05-7.78(3H,m), 7.60(1H,d,J=8.0 Hz), 7.50-7.25(4H,m),3.55-2.85(6H,m), 3.25(3H,s), 2.50(3H,s), 1.05(3H,t,J=7.0 Hz)

3-(N-Ethyl-N-propylamino)-2-(2-fluorophenyl)imidazo[2,1-a]isoquinoline(Compound 206)

IR(Neat): 3060, 2960, 2940, 2875, 1625, 1610, 1565, 1520, 1495, 1480,1456, 1418, 1378, 1260, 1220, 1175, 1150, 1115, 1090, 1030, 891, 820,790, 750, 696; NMR(CDCL): 8.82-8.10(1H,m), 8.03(1H,d,J=7.2 Hz),7.90-7.20(7H,m), 7.07(1H,d,J=7.2 Hz), 3.28-2.75(4H,m), 1.65-1.10(2H,m),1.04(3H,t,J=7.0 Hz), 0.81 (3H,t,J=7.0 Hz)

3-(N-Ethyl-N-propylamino)-6-isopentyl-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline(Compound 208) hydrochloride

m.p.: 149.0-151.5° C.; IR(KBr): 3060, 3020, 2960, 2940, 2875, 2550,2275, 1780-1770, 1651, 1615, 1605, 1539, 1495, 1465, 1455, 1422, 1384,1370, 1330, 1275, 1230, 1170, 1120-1060, 1040, 850, 825, 775, 723;NMR(CDCL): 9.95-9.70(1H,m), 8.20-7.78(4H,m), 7.50-7.25(4H,m),3.30-2.75(6H,m), 2.50(3H,s), 2.00-1.30(5H,m), 1.10(3H,t,J=8.0 Hz),1.10(6H,d,J=6.0 Hz), 0.90(3H,t,J=7.0 Hz)

3-(N-Ethyl-N-propylamino)-2-(3-methylphenyl)imidazo[2,1-a]isoquinoline(Compound 211) hydrochloride

m.p.: 152.5-156.0° C.; IR(KBr): 3060, 2980, 2940, 2860, 2600, 1656,1621, 1605, 1543, 1497, 1458, 1420, 1385, 1335, 1238, 1172, 1110-1088,890, 800, 750, 692; NMR(DMSO): 9.70-9.37(1H,m), 8.53(1H,d,J=7.0 Hz),8.40-7.24(8H,m), 3.25(4H,m), 2.46(3H,s), 1.70-1.10(2H,m),1.10(3H,t,J=7.0 Hz), 0.79(3H,t,J=7.0 Hz)

3-(N-Ethyl-N-propylamino)-2-(3-methyl-2-thienyl)imidazo[2,1-a]isoquinoline(Compound 212) hydrochloride

m.p.: 146.0-148.5° C.; IR(KBr): 3050, 2970, 2930, 2870, 2660-2590, 2330,1790, 1655, 1620, 1545, 1459, 1425, 1389, 1320, 1236, 1180, 1065, 890,800, 750; NMR(DMSO): 9.38-9.11(1H,m), 8.49(1H,d,J=7.0 Hz),8.32-7.74(5H,m), 7.18(1H,d,J=5.0 Hz), 3.17(2H,q,J=7.0 Hz),3.00(2H,t,J=7.0 Hz), 2.38(3H,s), 1.73-103(2H,m), 1.09(3H,t,J=7.0 Hz),0.80(3H,t,J=7.0 Hz)

3-[N-Ethyl-N-(3-methylthiopropyl)amino]-²-(2-methylphenyl)imidazo[2,1-a]isoquinoline (Compound 214)

IR(Neat): 3070, 2980, 2940, 2860, 1639, 1612, 1559, 1520, 1482, 1457,1376, 1234, 1156, 1045, 954, 895, 792, 750, 700; NMR(CDCL):8.82-8.55(1H,m), 8.02(1H,d,J=7.0 Hz), 7.75-7.21(7H,m), 7.06(1H,d,J=7.0Hz), 3.03(2H,q,J=7.0 Hz), 2.99(2H,t,J=7.0 Hz), 2.45(2H,t,J=7.0 Hz),2.35(3H,s), 1.98(3H,s), 1.98-1.47(2H,m), 1.06(3H,t,J=7.0 Hz)

3-(N-Ethyl-N-isopentylamino)-2-(2-ethylphenyl)imidazo[2,1-a]isoquinoline(Compound 216) hydrochloride

m.p.: 159.5-161.0° C.; IR(KBr): 3060, 2970, 2940, 2880, 2600, 1660,1621, 1550, 1494, 1465, 1424, 1390, 1339, 1290, 1250, 1229, 1165, 1100,890, 800, 750; NMR(DMSO): 9.20-8.98(1H,m), 8.49(1H,d,J=7.0 Hz),8.33-7.74(4H,m), 7.64-7.38(4H,m), 3.25-2.76(6H,m), 1.52-0.96(9H,m),0.80(6H,d,J=6.0 Hz)

3-[N-Ethyl-N-(4-methylbenzyl)amino]-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline(Compound 219)

IR(Neat): 3080, 3040, 2990, 2940, 2860, 1645, 1612, 1560, 1519, 1482,1458, 1380, 792, 750; NMR(CDCL): 8.80-8.50(1H,m), 8.05(1H,d,J=7.0 Hz),7.80-7.20(7H,m), 7.20-6.89(5H,m), 4.05(2H,s), 2.98(2H,q,J=7.0 Hz),2.26(6H,s), 1.00(3H,s) (hydrochloride m.p.: 116.0-119.0° C.)

3-[N-Ethyl-N-(4-methylbenzyl)amino]-2-(2-ethylphenyl)imidazo[2,1-a]isoquinoline(Compound 220)

IR(Neat): 3070, 3040, 2990, 2940, 2890, 1639, 1610, 1558, 1519, 1482,1455, 1420, 1372, 1270, 1230, 1160, 1020, 896, 840, 790, 700; NMR(CDCL):8.82-8.50(1H,m), 8.00(1H,d,J=7.4.0 Hz), 7.78-6.88(12H,m), 4.02(2H,s),2.98(2H,q,J=7.0 Hz), 2.62(2H,q,J=7.0 Hz), 2.26(3H,s), 1.22(3H,t,J=7.0Hz), 1.00(3H,t,J=7.0 Hz)

3-(N-Allyl-N-ethylamino)-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline(Compound 222) hydrochloride

m.p.: 175.0-178.0° C.; IR(KBr): 3100, 2990, 2580, 2400-2310, 1750, 1655,1620, 1542, 1498, 1420, 1233, 1100, 1082, 1010, 928, 891, 803, 750, 692;NMR(DMSO): 9.34-8.93(1H,m), 8.53(1H,d,J=7.0 Hz), 8.40-7.78(4H,m),7.49(4H,s), 6.18-5.52(1H,m), 5.38-4.88(2H,m), 3.68(2H,d,J=6.0 Hz),3.00(2H,q,J=7.0 Hz), 2.40(3H,s), 1.00(3H,t,J=7.0 Hz),

3-Ethylamino-2-(2-methylphenyl)imidazo[1,2-a]thieno[3,2-c]pyridine(Compound 340) hydrochloride

m.p.: 192.0° C.(sublimation); IR(KBr): 3150, 3060, 3030, 2970, 2910,2870, 2770, 2710, 2650, 2600, 1650, 1620,1600, 1533, 1495, 1422, 1379,1315, 1290, 1243, 1215, 1162, 1086, 1008, 959, 763, 721; NMR(DMSO):8.41(1H,d,J=5.8 Hz), 8.25(1H,d,J=4.0 Hz), 8.08-7.86(2H,m),7.63-7.20(4H,m), 2.97(2H,q,J=7.8 Hz), 2.48(3H,s), 1.01(3H,t,J=7.8 Hz)

3-Ethylamino-2-(2-methylphenyl)imidazo[1,2-a]thieno[2,3-c]pyridine(Compound 345) hydrochloride

m.p.: 237.0° C.(dec.); IR(KBr): 3140, 3050, 2960, 2910, 2860, 2780,2700, 2650, 2550, 1653, 1624, 1600, 1545, 1525, 1500, 1442, 1414, 1385,1353, 1323, 1280, 1248, 1205, 1150, 1095, 1057, 1040, 920, 840, 792,750, 733, 715; NMR(DMSO): 8.82(1H,d,J=7.0 Hz), 8.32(1H,d,J=5.0 Hz),7.94(1H,d,J=7.0 Hz), 7.80(1H,d,J=5.0 Hz), 7.66-7.33(4H,m),2.88(2H,q,J=7.0 Hz), 2.40(3H,s), 0.98(3H,t,J=7.0 Hz)

3-(N-Ethyl-N-propylamino)-2-(2-methylphenyl)imidazo[1,2-a]thieno[2,3-c]pyridine(Compound 356) hydrochloride

m.p.: 185.0-188.5° C.; IR(KBr): 3040, 2960, 2930, 2860, 2530, 2250,1650, 1613, 1570, 1538, 1490, 1457, 1410, 1386, 1350, 1320, 1278, 1242,1213, 1173, 1080, 1038, 803, 762, 730; NMR(DMSO): 8.70(1H,d,J=7.0 Hz),8.48(1H,d,J=5.0 Hz), 8.10(1H,d,J=7.0 Hz), 7.93(1H,d,J=5.0 Hz),7.55(4H,s), 3.10(2H,q,J=7.0 Hz), 2.93(2H,t,J=7.0 Hz), 2.44(3H,s),1.78-1.02(2H,m), 1.08(3H,t,J=7.0 Hz), 0.78(3H,t,J=7.0 Hz)

EXAMPLE 23

3-Amino-9-methoxy-2-(2-methylphenyl)-5,6-dihydroimidazo[2,1-a]isoquinoline(Compound 103)

To a solution of 8.4 g of3-amino-9-methoxy-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline(Compound26) in 100 ml of ethanol was added 1.0 g of palladium on activatedcarbon (Pd 10%). After introduction of hydrogen, the mixture was stirredat room temperature for 48 hours. The reaction mixture was filtered, andthe filtrate was evaporated in vacuo. Resultant residue was purified bycolumn chromatography on silica gel and recrystallized from ethylacetate/isopropyl ether to give 1.5 g of the title compound as a paleyellow powder.

m.p.: 159.5-160.0° C.; IR(KBr): 3460, 3340, 3200, 3070, 3020, 2930,2900, 2850, 1628, 1618, 1572, 1540, 1498, 1470, 1458, 1440, 1358, 1322,1283, 1230, 1180, 1035, 820, 770; NMR(CDCL): 7.58(1H,d,J=3.0 Hz),7.46-7.20(4H,m), 7.13(1H,d,J=9.0 Hz), 6.77(1H,dd,J=3.0 Hz,9.0 Hz),3.96(2H,t,J=7.0 Hz), 3.84(3H,s), 3.20(2H,brs), 3.04(2H,t,J=7.0 Hz),2.40(3H,s)

EXAMPLE 24

3-Amino-9-hydroxy-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline (Compound22).

To a solution of 5 g of3-amino-9-benzyloxy-2-(2-methylphenyl)imidazo[2,1-a]isoquinoline(Compound 40) in 100 ml of ethanol was added 0.5 g of palladium onactivated carbon (Pd 10%). After introduction of hydrogen, the mixturewas stirred at room temperature for 24 hours. The reaction mixture wasfiltered, and the filtrate was evaporated in vacuo. Resultant residuewas purified by column chromatography on silica gel and recrystallizedfrom water/methanol to give 3.2 g of the title compound as pale yellowneedles.

m.p.: 240.0-243.0° C.(dec.); IR(KBr): 3400, 3320, 3000-2450, 1610, 1490,1455, 1420, 1395, 1325, 1255, 1232, 1200, 1130, 1080, 1030, 920, 865,815, 758, 720; NMR(DMSO): )10.00(H,brs), 7.92(1H,d,J=7.0 Hz),7.77(1H,d,J=2.0 Hz), 7.68(1H,d,J=8.4 Hz), 7.65-6.90(5H,m),7.09(1H,d,J=7.0 Hz), 4.92(2H,brs), 2.45(3H,s)

Pharmaceutical formulation 1: Powders containing3-amino-5-methyl-2-(2-methylphenyl)imidazo[1,2-a]thieno[3,2-c]pyridine(Compound 236) as an active ingredient

Five grams of3-amino-5-methyl-2-(2-methylphenyl)imidazo[1,2-a]thieno[3,2-c]pyridine(Compound 236) and 95 g of lactose were admixed uniformly to give thepowders.

Pharmaceutical formulation 2: Granules containing3-amino-5-methyl-2-(2-methylphenyl)imidazo[1,2-a]thieno[3,2-c]pyridine(Compound 236) as an active ingredient

Five grams of3-amino-5-methyl-2-(2-methylphenyl)imidazo[1,2-a]thieno[3,2-c]pyridine(Compound 236), 36 g of lactose, 31 g of corn starch, and 22 g ofcrystalline cellulose were admixed, and then the resultant powder wasgranulated by kneading it with 4 g of hydroxypropylcellulose in 100 mlof water, and the resultant grains were dried for 4 hours at 50° C. Thedried grains were sifted through a 12 mesh sieve, and mixed with 2 g ofmagnesium stearate to obtain granules.

Pharmaceutical formulation 3: Tablets containing3-amino-5-methyl-2-(2-methylphenyl)imidazo[1,2-a]thieno[3,2-c]pyridine(Compound 236) as an active ingredient

Five grams of3-amino-5-methyl-2-(2-methylphenyl)imidazo[1,2-a]thieno[3,2-c]pyridine(Compound 236), 35 g of lactose, 32 g of corn starch, and 24 g ofcrystalline cellulose were admixed, and then the resultant powder wasgranulated by kneading it with an aqueous solution containing 2 g ofhydroxypropylcellulose, and then the granules were dried for 4 hours at50° C.

After mixing with 2 g of magnesium stearate, the granules werecompressed into tablets, each weighing 200 mg, using a tablet machine.

Pharmaceutical formulation 4: Capsules containing3-amino-5-methyl-2-(2-methylphenyl)imidazo[1,2-a]thieno[3,2-c]pyridine(Compound 236) as an active ingredient

Five grams of3-amino-5-methyl-2-(2-methylphenyl)imidazo[1,2-a]thieno[3,2-c]pyridine(Compound 236), 38 g of lactose, 33 g of corn starch, 22 g ofcrystalline cellulose, and 2 g of magnesium stearate were admixed. Themixture was filled into hard gelatin capsules, each weighing 200 mg,using a capsule filler.

Pharmaceutical formulation 5: Syrups containing3-amino-5-methyl-2-(2-methylphenyl)imidazo[1,2-a]thieno[3,2-c]pyridine(Compound 236) as an active ingredient

One gram of3-amino-5-methyl-2-(2-methylphenyl)imidazo[1,2-a]thieno[3,2-c]pyridine(Compound 236), 30 g of sucrose, 25 g of D-sorbitol(70 w/v %), 30 mg ofethyl p-hydroxybenzoate, and 15 mg of propyl p-hydroxybenzoate weredissolved in 60 g of warm water. After cooling, a flavouring dissolvedin 150 mg of glycerin and 500 mg of ethanol(96%) was added thereto.Water was added to the mixture to give 100 ml of syrups.

We claim:
 1. Fused imidazo[1,2-a]pyridines represented by the following general formula (I): ##STR16## wherein ring A represents an aromatic ring selected from benzene, thiophene, furan or pyrrole ring; any one of Z¹, Z², or Z³ represents a sulfur atom with the other two Z groups being carbon; R¹ is a hydroxyl group, halogen atom, lower alkyl group which may be halogenated, lower alkoxy group or acyloxy group;k represents 0, 1, 2 or 3; R² and R³ may be the same or different and each represent a hydrogen atom, alkenyl group, acyl group, alkoxycarbonyl group or lower alkyl group which may have substituent(s) selected from the group consisting of 1) halogen atom, 2) hydroxyl group, 3) lower alkoxy group, 4) lower alkylthio group, 5) alkylsulfinyl group, 6) alkoxycarbonyl group, 7) carbamoyl group, 8) alkylamino group and 9) aryl group, or R² and R³, together with the nitrogen atom to which they are attached, may form a 5- or 6-membered monocyclic heterocyclic ring, or R² and R³, together with the nitrogen atom to which they are attached, may form an alkylideneamino group or arylalkylideneamino group; R⁴ and R⁵ each independently represent a halogen atom, cyano group, hydroxyl group, carboxyl group, alkoxycarbonyl group, acyl group, alkylamino group, aryl group, acyloxy group, carbamoyloxy group, lower alkyl group which may have substituent(s) selected from the group consisting of 1) hydroxyl group, 2) lower alkoxy group, 3) aryl group and 4) aryloxy group, lower alkoxy group which may have substituent(s) selected from the group consisting of 1) hydroxyl group, 2) lower alkoxy group, 3) lower alkoxycarbonyl group and 4) aryl group, or lower alkylthio group which may be substituted with an aryl group; R⁶, which may be present or absent, is selected from the group consisting of a halogen atom, lower alkyl group which may be halogenated, or lower alkoxy group; m represents 0, 1 or 2; n represents 0, 1 or 2; the dotted line, together with the solid line, represents a single or double bond, provided that plural R⁴ s may be attached to the same carbon atom, or a pharmaceutically acceptable salt or solvate thereof.
 2. The compounds of claim 1 whereinR² and R³ may be the same or different and each represent hydrogen atom, alkenyl group or lower alkyl group which may have substituent(s) selected from the group consisting of halogen atom, lower alkoxy group, lower alkylthio group and aryl group, or R² and R³, together with the nitrogen atom to which they are attached, may form a 5- or 6-membered monocyclic hetrocyclic ring.
 3. The compounds of claim 1 wherein ring A is an aromatic ring selected from benzene, thiophene, furan or pyrrole ring;R¹ is halogen atom or lower alkyl group which may be halogenated or lower alkoxy group; k is 1 or 2; R² is hydrogen atom; R³ is hydrogen atom, alkenyl group or lower alkyl group which may have substituent(s) selected from the group consisting of halogen atom, lower alkoxy group, lower alkylthio group and aryl group.
 4. The compounds of claim 3 wherein the dotted line, together with the solid line, represents a double bond.
 5. The compounds of claim 4 wherein ring A and substituent(s) on the ring represent the following formula: ##STR17## wherein R¹ and R⁶ are each independently halogen atom, lower alkyl group which may be halogenated or lower alkoxy group; k' is 0 or 1; Z is a hetero atom selected from sulfur, oxygen or nitrogen atom.
 6. The compounds of claim 5 wherein at least one of R¹ and R⁶ is lower alkyl group.
 7. The compounds of claim 6 wherein R⁶ is lower alkyl group having 1 or 2 carbon atoms; R⁴ and R⁵ are each independently a substituent selected from halogen atom, lower alkyl group, lower alkoxy group or lower alkylthio group.
 8. The compounds of claim 1 wherein ring A is an aromatic ring selected from benzene, thiophene, furan or pyrrole ring represented by the following formula: ##STR18## wherein k¹ is 0 or 1; Z is a hetero atom selected from a sulfur, oxygen or nitrogen atom;the substituent R¹ on the ring is halogen atom, lower alkyl group which may be halogenated, or lower alkoxy group; R² and R³ are hydrogen atoms; R⁴ and R⁵ are independently a substituent selected from a halogen atom, lower alkyl group, lower alkoxy group or lower alkylthio group; m is 0, 1 or 2; n is 0, 1 or 2; and the dotted line, together with the solid line, represents a double bond.
 9. Pharmaceutical compositions containing the compound defined in claim 1, in association with a pharmaceutically acceptable carrier.
 10. Pharmaceutical compositions according to claim 9 comprising an amount of the compound effective for the treatment of gastrointestinal diseases.
 11. Pharmaceutical compositions according to claim 9 comprising an amount of the compound effective for treating an ulcer.
 12. A method of treating a patient suffering from gastrointestinal diseases including ulcer, which comprises administering an effective amount of a compound defined in claim 1 to the patient. 